1. The birth of ROP:
Retinopathy of prematurity ROP was born as a corollary of improved neonatal care when smaller/ more premature babies began to survive with oxygen support. While a number of risk factors have been studied, prematurity and oxygen have emerged as major driving factors in the pathogenesis of ROP.
Animal models have provided deeper insights into understanding this relatively new blinding disease in mankind.
2. The Burden:
An estimated 13.4 million babies were born preterm in 2020, of which 3.02 million were from India, accounting for over 23% of all preterm births worldwide. [1,2] Also, in India, it is not uncommon for heavier and older babies to develop treatment‑requiring ROP, unlike in the developed countries, due to the more rampant use of unregulated oxygen as a lifesaving measure.[3] With this, the burden of retinopathy of prematurity (ROP) screening has increased tremendously in the backdrop of a preexisting strained doctor‑to‑preterm child ratio with <1% ophthalmologist of the country engaged in ROP care. The available care is unevenly distributed with rural population having very less access to screening and treatment facilities. All these factors have made ROP an emerging public health problem in India.
3. Guidelines for screening:
The Screening guidelines of our country are according to the Rastriya Bal Swasthya Karyakram (RBSK) -2017 and National Neonatology Forum (NNF) -2020. Babies requiring ROP screening include: Birth weight <2000g, gestational age < 34 weeks, or gestation age 34 to 36 weeks of gestation with other risk factors including respiratory support, oxygen therapy for more than 6 h, sepsis, episodes of apnea and need of blood transfusion, exchange transfusion, unstable clinical course as determined by pediatrician.
4. ROP Screening:
The first screening should be done by 4 weeks of birth. In case of extreme prematurity (gestational age <28 weeks or birth weight <1200 grams) screening should be done earlier, by 3 weeks of birth. The screening includes dilated fundus examination using ROP drops (prepared by mixing 2.5 ml of tropicamide phenylephrine combination with 2.5ml tear substitute). All extra eye drops to be wiped off to prevent systemic absorption through skin. Withhold feeding for atleast 40 minutes prior to screening is recommended. Swaddling the baby during the screening increases ease. Topical anesthetic 0.5 % proparacaine instilled. Alphonso speculum used to keep lids apart and a vectis is used to rotate globe and for scleral indentation. Indirect ophthalmoscopy with 28D lens (or 20D) is used to see posterior pole, and atleast nasal and temporal periphery. Topical antibiotics instilled at the end. Documentation must be done including zone, stage, plus disease according the latest guidelines [4] with a follow up date. Documentation to preferably include a diagram and photographic documentation (using Retcam, NeoForus, or smartphone-based cameras) to be done wherever possible.
To overcome the burden of screening, telescreening is also an effective method of screening where trained technicians take images of the fundus and send to base hospital where reporting is done real time by a ROP expert and only treatment requiring babies are referred to base hospital.
5. Clinical reg flags:
The presence of plus disease forms the hallmark of treatment requiring ROP. Venous dilatation and arterial tortuosity of the posterior pole (Vessels within zone I) indicate the presence of plus disease [4] Aggressive ROP (AROP) is defined as abnormal dilation and tortuosity of the vessels in Zone I and posterior zone II with deceptively featureless demarcation between vascularized and non-vascularized retina with loops/ flat network of neovascularization on the retinal surface. Rapidly progress to Stage 5 disease without traversing the classical course from Stages 1 to 3, and require immediate treatment/ referral.
6. Treatment- laser and intravitreal injections:
Laser photocoagulation is an effective treatment option in ROP and works by ablating the peripheral avascular retina that is the source of the high VEGF. It has been the historic gold standard for treatment of ROP. Green laser or red can be used for the treatment. While green laser causes lesser pain, red laser had better penetration through hazy media. The side effects of high myopia and peripheral field defects. Anti VEGF injections work by suppressing the extremely high VEGF load in the vitreous cavity that not only regresses the ROP but promotes physiological vascularization until the effect of the Anti VEGF lasts in the eye, beyond which the disease can recur unless the vascularization is complete upto ora. Anti VEGFs come with the concerns of systemic VEGF suppression. Also, anti VEGF treated eyes often need additional laser at a later date. The dose of intravitreal Anti VEGF in ROP babies is half (or even lesser) of adult dose. [5] For AROP and zone 1 (Posterior diseases), and sick babies who may not be able to withstand laser, anti VEGFs are the treatment of choice. While for peripheral diseases either treatment options are used.
7. ROP surgery:
ROP surgeries are required when tractional detachments involving part of or the entire retina (stage 4A,B, 5). ROP surgeries are challenging due to the small size of the eye with a relatively large lens which makes instrumentation difficult in a crowded space. The principles include:
Identifying the vector forces causing the tractional detachment
Planning the surgical approach [vitrectomy (LSV), lensectomy (L), Buckling (BB) or any combination of these procedures)
Planning a safe access (which in stage 5 requires lensectomy and entry through limbus or iris route
Relieving the traction (as many vectors possible) without creating any iatrogenic breaks.
8. Rehabilitation:
Rehabilitation forms the backbone for the success of ROP treatment and helps to maximize the vision potential
It includes
- Correcting the myopia early (myopia of prematurity / laser induced myopia)
- Correcting the high hyperopia due to aphakia in surgical cases
- Starting early Visual stimulation exercises (separate training in form sense, colour sense, binocular single vision– as applicable depending on the visual potential)
- Low vision related training – low vision aids, education in Braille and vocational training
9. Realistic expectations, response and follow up
In stage 4 ROP, anatomical success is defined as macular attachment. Vision is often recorded initially as visual behavior like fixing and following light. However, these babies are expected to achieve visual acuity that can be quantitative later assessed on a Cardiff chart. In stage 5 surgery, the aim is to achieve any retinal attachment and give atleast ambulatory vision. Response is initially recorded as fixing and following light. In a large study including 202 eyes, 50.5% eyes achieved anatomical success (74% -Stage 4a and 4b and 33% -Stage 5) Favorable anatomical outcome were Stage 4 disease (vs. Stage 5), prior treatment (laser ± anti-VEGF), surgery with 25G MIVS (vs. 23G) and LSV (vs. LV), retinal break was significantly associated with poor anatomical outcome. Close follow up for glaucoma is also needed in these eyes. [6]
10.Future directions:
Retinopathy of Prematurity (ROP) serves as a compelling example of how Artificial intelligence (AI) can revolutionize the field of medicine.AI is taking ROP care a step forward by potentially addressing the issue of handling the burden of ROP screening. AI's integration into ROP management spans from risk prediction, diagnosis, and severity assessment, to reducing expert disagreements, guiding clinical decisions, determining intervention timing, monitoring progression, identifying recurrences. [7] Despite a few pitfalls, AI has the potential to develop into a widely implemented system that could reduce the dependence on human resources for screening the large at‑risk population, significantly reduce the cost of screening, and provide epidemiologic insights for standardizing and improving neonatal and ROP care in the country. However, it needs to be validated prospectively in a large population of preterm babies.
ROP is one of the leading causes of preventable blindness in children worldwide, with it becoming a public health problem in India. Multiple aspects of ROP management are challenging, including logistic difficulties of rural population to avail care, the high risk in anesthesia for the sick babies, poor surgical outcomes in stage 5 and emerging medicolegal problems for pediatricians and ophthalmologist.