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Nov 2013

Retinopathy of Prematurity - Middle East/North Africa

Europe

EPIDEMIOLOGY

Global Information

Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness in middle-income countries (Gilbert, 2008).
ROP occurs primarily in infants of low birth weight and low gestational age at birth.
Most studies report ROP incidences that are about 60% for babies less than 1500 g (Zin and Gole, 2013).
The worldwide prevalence of blindness due to ROP is approximately 50,000.
One of the greatest challenges in less-developed countries is having adequate screening done by ophthalmologists trained to diagnose ROP with indirect ophthalmoscopy. Telemedicine with the use of digital imaging and fundus photography may also be a potential strategy for ROP screening in regions where there are few trained ophthalmologists who can manage ROP.

Region-Specific Information (Africa/Middle East)

Table 1. Incidence of severe ROP in Africa/Middle East
Country	Definition of Severe ROP	Severe ROP Incidence
Kuwait	Treatable ROP	7.8%
Saudi Arabia	Treatable ROP	1.2 – 6.4%
Iran	ROP any stage	8.5%
South Africa	Treatable ROP (CRYO-ROP)	4.3%

DIFFERENTIAL DIAGNOSIS

Familial exudative vitreoretinopathy (FEVR)/Norrie (Figure 1)
Coats disease (Figure 2)
Persistent fetal vasculature (formerly persistent hyperplastic primary vitreous (Figure 3)
Retinoblastoma (Figure 4)
Incontinentia pigmenti (Figure 5)
Peripheral uveitis/pars planitis (Figure 6)

PATHOPHYSIOLOGY/DEFINITION

Chart 1. Pathophysiology/Definition. See the Image Library for selected figures.

The following factors may play a role in ROP. They have been shown to be angiogenic in ischemia-induced retinopathies:

Insulin-like growth factor I (IGF-I)
Growth hormone
Angiopoietin (Suri, Jones et al, 1996; Sarlos, Rizkalla et al, 2003)
Platelet-derived growth factor-β (PDGF-β)

Major Risk Factors

Prematurity
Low birth weight
Hyperoxia

SIGNS, SYMPTOMS

Advanced cases can present with:

Leukocoria (secondary to retinal detachment)
Strabismus

MANAGEMENT

Diagnosis of ROP is made by sequential examinations, indirect ophthalmoscopy, and by digital imaging.

The International Classification of ROP (ICROP) includes 5 parameters:

(1) Zone: The location of the disease in the retina (Figure 12)

Zone I is the posterior retina within 60 degrees of the optic disc

Zone II is a concentric circle extending from Zone 1 to the nasal ora serrata

Zone III is the remaining temporal retina

(2) Clock hours: The extent of the developing vasculature that is involved quantified from 1-12 clock hours

(3) Stage: The severity of the abnormal vascular changes observed

Stage 1: Demarcation line between vascularized and non-vascularized retina (Figure 13)

Stage 2: Demarcation line w/ elevation (Figure 14)

Stage 3: Demarcation line with fibrovascular proliferation (Figure 15)

Stage 4a: Partial detachment of retina not involving fovea (Figure 16)

Stage 4b: Partial detachment of retina involving fovea (Figure 17)

Stage 5: Total retinal detachment (Figure 18)

(4) Plus disease: Venular dilation and arteriolar tortuosity in the posterior pole
(Figure 19)

(5) Pre-plus disease Abnormal-appearing vasculature that does not make criteria for Plus disease (Figure 20)

Aggressive posterior ROP (AP-ROP) is a severe form of ROP that rapidly causes total retinal detachment without going through the normal stages of ROP (Figure 21).

AP-ROP (zone I or -posterior zone II) needs especially close follow-up.

Screening

The Revised Joint Policy Statement issued in 2013 by the American Academy of Pediatrics, the American Association of Pediatric Ophthalmology and Strabismus, and the American Academy of Ophthalmology provides guidelines on screening and follow-up of premature neonates (Table 2).
Indications for screening are region dependent. Those in Table 2 are guidelines by American physicians.
In the United States premature neonates are examined for ROP if they have a birth weight of less than or equal to 1500 g or a gestational age of 30 weeks or less. Select infants with a birth weight between 1500 g and 2000 g or a gestational age at birth of greater than 30 weeks with an unstable clinical course should also have an eye exam.

Table 2. Screening Guidelines for Retinopathy of Prematurity
Screening Interval	Disease Features
1 week or less follow-up	Zone I retinal vessels ending without ROP, stage 1 or 2 ROP Zone II, Stage 2 or 3 ROP
1 to 2 week follow-up	Zone I, regressing ROP Zone II, Stage 1 ROP
2 week follow-up	Zone II, Stage 1 or regressing ROP
2 to 3 week follow-up	Zone II, immature vascularization without ROP Zone III, Stage 1 or 2 or regressing ROP

TREATMENT

Treatment is based on 2 multicenter trials: the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) trial and the Early Treatment for Retinopathy of Prematurity (ETROP) trial (CRYO-ROP Cooperative Group, 1988 and ETROP Cooperative Group, 2008)
Laser photocoagulation is the preferred treatment of choice. If laser is not available, cryotherapy may be performed.
Laser photocoagulation is performed when ROP reaches type 1 pre-threshold disease. See Table 3.
It is important to diagnose aggressive posterior ROP (AP-ROP) and treat it immediately, as this form of ROP can rapidly progress to retinal detachment.

Table 3. Disease Features of Pre-threshold Disease in Retinopathy of Prematurity
Type 1 ROP	Zone I, any stage ROP with Plus disease Zone I, Stage 3 ROP without Plus disease Zone II, Stage 2 or 3 ROP with Plus disease
Type 2 ROP	Zone I, Stage 1 or 2 ROP without Plus disease Zone II, Stage 3 ROP without Plus disease

Anti-VEGF Injections

Intravitreal injections of anti-vascular endothelial growth factor (Anti-VEGF) may cause rapid resolution of AP-ROP (Mintz-Hittner et al., 2011). However, laser photocoagulation remains the standard of care for most cases of treatment requiring ROP.

Surgery

If laser or cryotherapy fails to prevent progression of ROP and the patient develops a retinal detachment, surgery (vitrectomy, scleral buckle) may be performed.
Results are best when done before the fovea has detached.
Stage 5 ROP has a poor visual prognosis

Follow-Up

Patients with a history of ROP have a higher incidence of astigmatism, high myopia, and retinal detachment and should be followed routinely.

IMAGE LIBRARY

Differential Diagnosis

Figure 5. Incontinentia pigmenti. (Reproduced, with permission, from Lueder GT. Pediatric Ophthalmology and Strabismus.Basic and Clinical Science Course, Section 6, American Academy of Ophthalmology, 2013–2014.)

Figure 6. Peripheral uveitis/pars planitis. (Reproduced, with permission, from Lueder GT. Pediatric Ophthalmology and Strabismus.Basic and Clinical Science Course, Section 6, American Academy of Ophthalmology, 2013–2014.)

Pathophysiology/Definition

Figure 7. Peripheral retina ischemia. (Courtesy of Sjakon G. Tahija, SpM.)

Figure 8. Tortuosity and dilation of the vessels in the posterior pole (Plus disease). (Courtesy of Sjakon G. Tahija, SpM.)

Figure 9. Neovascularization. (Courtesy of Sjakon G. Tahija, SpM.)

Figure 10. Extraretinal fibrovascular proliferation. (Courtesy of Sjakon G. Tahija, SpM.)

Figure 11. Retinal Detachment. (Courtesy of Sjakon G. Tahija, SpM.)

Management

Figure 12. Zones depict the location of the disease in the retina. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 13. International Classification of ROP, Stage 1. Demarcation line between vascularized and vascular retina. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 14. International Classification of ROP, Stage 2. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 15. International Classification of ROP, Stage 3. Extraertinal fibrovascular proliferation. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 16. International Classification of ROP, Stage 4a. Partial detachment of the retina not involving the fovea. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 17. International Classification of ROP, Stage 4b. Partial detachment of the retina involving the fovea. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 18. International Classification of ROP, Stage 5. Total retinal detachment. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 19. Pre-plus disease. Abnormal-appearing vasculature that does not meet criteria for Plus disease. (Courtesy of R.V. Paul Chan, MD, FACS and Michael F. Chiang, MD.)

Figure 20. Aggressive Posterior ROP (AP-ROP)is a severe form of ROP that rapidly causes total retinal detachment without going through the normal stages of ROP. (Courtesy of Sjakon G. Tahija, SpM.)

REFERENCES

Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol. 2013;40:185-200.

CONTRIBUTORS

Section Editors:
North Africa/Middle East:
Ebtisam S. Kadhem Al-Alawi, FRCS, MRCOpht, DO, Salmaniya Medical Center, Bahrain

Assistant Editors:
Swetangi D. Bhaleeya, MD, Weill Cornell Medical College; New York, New York
Kristin Chapman, MD, Weill Cornell Medical College, New York, New York
Peter Coombs, MD, Weill Cornell Medical College; New York, New York
Michael Klufas, MD, Weill Cornell Medical College, New York, New York
Samir Patel, medical student, Weill Cornell Medical College; New York, New York

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Navigate This Guideline

EPIDEMIOLOGY

Global Information

Region-Specific Information (Africa/Middle East)

Screening

Anti-VEGF Injections

Surgery

Follow-Up

IMAGE LIBRARY

Differential Diagnosis

Pathophysiology/Definition

REFERENCES

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