Retinopathy of Prematurity.
Pediatric Retina & Ocular Oncology Department, Aravind Eye Hospital & Postgraduate Institute of Ophthalmology, Coimbatore - 641014, Tamil Nadu.
E-mail: drshahpk2002@yahoo.com
Introduction
Retinopathy of Prematurity (ROP) is a fibrovascular proliferative disorder, which affects the developing peripheral retinal vasculature of premature infants. It is an avoidable cause of blindness in children.
The initial signs of ROP are detectable by a few weeks after birth, and the condition progresses rapidly thereafter. This means that screening has to be timely, and there is only a very narrow window of opportunity for treating. If not treated, the condition progresses rapidly to Stage 4 or 5 in approximately 50% of babies. The visual prognosis for babies with Stage 5 disease (total retinal detachment) is very poor, even after complex vitreoretinal surgery. The primary goal of screening is to detect all babies with treatable disease in time for treatment to be effective.
Pathogenesis
In the normal foetus, vascular development of the retina occurs in two phases.
Phase 1 (True vasculogenesis): It occurs from 8-21 weeks of foetal development. Spindle cells (mesenchymal precursor cells) appear around optic disc region. Then cords of spindle cells advance towards ora serrata which differentiate into capillaries which subsequently develop into arterioles and venules. Phase 1 is not under the control of Vascular Endothelial Growth Factor (VEGF)
Phase 2 (Angiogenesis): Occurs from 22 to 40 weeks of development. Proliferating endothelial cells migrate from existing blood vessels to form new capillaries. Phase 2 is VEGF dependant
Angiogenesis are of 2 types:
Physiologic Angiogenesis: As vascularization is incomplete at birth in preterm infants, the avascular anterior retina causes physiologic hypoxia & VEGF release. Thus immature vessels grow normally
Pathologic Angiogenesis (ROP pathogenesis): When child is exposed to high oxygen after birth there is down regulation of VEGF. This leads to vaso-obliteration & cessation of vessel growth. When oxygen exposure is reduced there is a pathological release of VEGF from now larger avascular retina that leads to neovascularization
Thus, changes in local tissue oxygen level are believed to be important to normal retinal vascular development through the effect of growth factors. If VEGF production persists then the ROP will progress. But if VEGF levels decrease then regression of ROP can occur
Risk factors
Three crucial risk factors:
- Birth weight
- Gestational age
- Number of days oxygen administered
No consensus is present on which of these criteria should be used, either alone or in combination for screening of ROP.
Other risk factors:
- Multiple births
- Blood transfusions
- Respiratory Distress Syndrome (RDS)
- Sepsis
- Intra Ventricular Hemorrhage (IVH)
- Intra Uterine Growth Retardation (IUGR)
- Vit E deficiency
- Anemia
- Seizures.
Screening
When to screen? When should a pediatrician refer to ophthalmologist for ROP screening?
Ideally babies are to be screened at 31 weeks post conceptional age (gestational age + post natal age) or 4 weeks after birth, whichever is later.1 However, an easier way to remember is that first retinal examination should be done by first month of life.
Whom to screen?
Screening all premature babies will be a waste of time, as we know that all do not develop ROP. UK guidelines state that babies with gestational age (GA) £ 31 weeks or birth weight (BW) £ 1500 g should be screened for ROP. USA guidelines are GA £ 30 weeks or BW £ 1500 g. We cannot follow the western screening guidelines as in the Indian scenario we still see bigger babies getting severe ROP. So, for the Indian scenario all babies having GA £ 35 weeks or having BW £ 1800 g should be screened for ROP. Apart from this, babies that fall outside the screening guidelines but have a rough course in neonatal intensive care unit (NICU) should also be screened at the pediatrician’s discretion. This is called “sickness criteria”.
Video: Showing Screening of premature baby (Click right and select rewind to see the video from begining)
How to screen?
A retina specialist or a pediatric ophthalmologist does screening. It is done with the help of indirect ophthalmoscope, 28 D lens, scleral depressor (wire vectis) and alphonso speculum. 0.5% proparacaine drops are used for topical anesthesia and half strength tropicamide plus (0.4% tropicamide with 2.5% phenylephrine) is used for pupillary dilatation. Recently, a new digital camera, Retcam, is available for screening but is a very expensive tool. It is the duty of the pediatrician to call these trained ophthalmologists to their NICU or they should refer the children to them at end of first month. ROP screening should be included as a part of neonatal care.
Figure 1:Retcam
Examinations via binocular indirect ophthalmoscope for ROP are difficult and require doctors with specialized paediatric retina training. Moreover hand drawn sketches are the only means of documentation for infant retina, which has its own disadvantages.
RetCam is a digital camera for imaging the retina of infants. It is a mobile self-contained system that can move easily around the hospital or office. It provides state-of the art wide field pediatric retinal imaging (130 degrees). It has instant & accurate documentation, avoiding time-consuming retinal drawings
In just a few minutes one can do an entire exam and the images are stored permanently on a 9.4 GB DVD. It allows easy accessible imaging even by non-ophthalmologists (NICU nurses) and also allows the transmission of these digital images to centers where ROP expertise is available via telemedicine. It provides 24-bit color, mega-pixel digital images, presented on a 17- inch computer monitor available for printout or electronic transmission. Thus it serves as a good teaching tool for others. Comprehensive database keeps track of each image, session and patient allowing for later side-by-side comparison of the case images. FFA can also be done. Newer Retcam II & III have the same features but with a flat screen monitor. Retcam shuttle is laptop based.
Video: Retcam (Click right and select rewind to see the video from begining)
Disadvantages of Retcam : Imaging of infant retina till ora in not possible without scleral depression and it is a very expensive tool.
Classification of ROP
An international classification of retinopathy of prematurity was published in 1984 and updated in 1987 and 2005.2-4 The components of classification is as follows.
- Location of disease: Each eye is divided in three zones to define the exact location.
- Zone I - circle, the radius of which extends from the disc to twice the distance from the disc to the fovea.
- Zone II – extends from the edge of zone I peripherally to ora serrata nasal and equivalent area near the temporal equator
- Zone III – residual crescent of retina anterior to zone II temporally
- Extent of disease: In the form of no. of clock hours involvement (Figure 2)
Figure 2: Schematic diagram of right eye (RE) and left eye (LE) showing zones to describe location of disease and clock hours to describe extent of ROP.
- Staging of disease: Is done according to degree of vascular changes. Each stage is defined by its location in zone & extent in clock hours for documentation.
- Stage 1 – Demarcation Line: This line is a thin but definite structure that separates the avascular retina anteriorly from the vascularized retina posteriorly. The demarcation line is relatively flat, white, and lies within the plane of the retina (Figure 3).
Figure 3: Retcam picture of RE showing stage 1 demarcation line (black arrows).
- Stage 2 – Ridge: The ridge is the hallmark of stage 2 ROP. It arises in the region of the demarcation line, has height and width, and extends above the plane of the retina (Figure 4).
Figure 4: Retcam picture of LE showing stage 2 elevated ridge (black arrows).
