Delhi Journal of Ophthalmology

Aggressive Posterior Retinopathy of Prematurity (APROP): A Preventable Challenge

Dr. Parijat Chandra (MD, DNB)
Professor of Ophthalmology
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences (AIIMS), 
New Delhi, India

Corresponding Author:

Dr. Parijat Chandra (MD, DNB)
Professor of Ophthalmology
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences (AIIMS), 
New Delhi, India

Published Online: 08-OCT-2020



Keywords :

Aggressive posterior retinopathy of prematurity (APROP)  is a severe variant of retinopathy of prematurity (ROP)1 which is observed in very preterm low birth weight babies exposed to poor neonatal care with unregulated oxygen and systemic risk factors. Clinically, APROP confuses beginners and experts alike, and a high index of suspicion is necessary if APROP has to be detected and treated in time to prevent poor outcomes.

APROP occurs in zone 1 or zone 2 posterior and the profile varies significantly from classical staged ROP. It has an unclear vascular-avascular junction with plus disease out of proportion to the severity seen at the junction, often accompanied by multiple vascular loops enclosing avascular areas. In severe cases involving posterior zone 1 ROP, even the macula may not be vascularized, with few vascular loops around the disc. The disease can rapidly progress to advanced retinal detachment and blindness. Therefore, as per national guidelines, ROP screening of preterm babies (<34 weeks gestation and <2000g birth weight or higher with risk factors) is very essential at 4 weeks of life (or as early as 2-3 weeks of life in very preterm babies <28 weeks gestation and <1200g birth weight) to detect ROP in time for effective subsequent management.2 

Laser photocoagulation of the avascular retina has been a time-tested treatment modality for decades, even for zone 1 ROP. However, a trained expert is needed to laser such extensive retinal areas and also inside multiple vascular loops to minimize skip areas for effective disease regression. This extensive laser can also lead to severely constricted visual fields and high refractive errors. But the disease can be relentless and despite the best laser treatment, disease progression can still occur.3 

The management of APROP has dramatically changed over the last few years with increased usage of intravitreal anti-VEGF drugs like Bevacizumab and Ranibizumab.  These drugs have significantly improved outcomes and are now rapidly emerging as the first-line treatment of APROP. They cause fast disease regression (especially in cases with extensive neovascularization) with the added benefit that the retina continues to vascularize into the periphery, with larger visual fields and less refractive errors. They also facilitate rapid pupillary dilation allowing early fundus assessment and quick use of other treatment options like laser/surgery if required. Supported by recent results of the RAINBOW trial,4 Ranibizumab received regulatory approval for ROP in the European Union. 

The commonest clinical challenge after anti-VEGF injection is ROP recurrence at around 6-8 weeks and warrants a longer regular follow-up so that secondary laser/injection may be performed if needed. There is also limited evidence in the literature about long term safety with risks of systemic drug absorption; limited knowledge about which drug is best, how many injections to use, and what is the most effective dose to give (although half adult dose is mostly used).5 There are new emerging challenges related to injection techniques like iatrogenic lens injury with cataract development or endophthalmitis caused due to injections in non-sterile environments. Though these drugs are expensive, support by government programs like Janani Shishu Suraksha Karyakaram (JSSK) makes them very affordable.

APROP is an important marker of the quality of care provided in the NICU. It is well known that severe ROP (and especially APROP) can be prevented if the best NICU practices are followed to prevent, minimize, and effectively manage ROP risk factors.6 The occurrence of severe ROP and APROP requiring treatment is very low in inborn NICU babies when the high quality of care is provided.7 A lot of resources are needed to manage every case of APROP, and yet the outcome can be unpredictable and poor, which might lead to medicolegal issues as well. Therefore, if ROP specialists get repeated referrals for APROP from specific NICU’s, it is worth discussing this with the pediatric teams, else such referrals and their resultant challenges will continue. Every effort must be made to ensure that best NICU practices are followed to prevent APROP. This will go a long way to prevent ROP related blindness.  

  1. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005 Jul;123(7):991–9. 
  2. Guidelines for Universal Eye Screening in Newborns Including Retinopathy of Prematurity [Internet]. Rashtriya bal swasthya karyakram; 2017 [cited 2020 Jul 1]. Available from:
  3. Chandra P, Tewari R, Jain S. The restless retina in aggressive posterior retinopathy of prematurity: prevention is better than cure. Community Eye Health. 2018;31(101):S27–8. 
  4. Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet Lond Engl. 2019 Sep 12.
  5. Sankar MJ, Sankar J, Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev. 2018 08;1:CD009734. 
  6. Sivanandan S, Chandra P, Deorari AK, Agarwal R. Retinopathy of Prematurity: AIIMS, New Delhi Experience. Indian Pediatr. 2016 Nov 7;53 Suppl 2:S123–8. 
  7. Sachan A, Chandra P, Agarwal R, Vohra R, Chawla R, Sankar MJ, et al. Profile of Retinopathy of Prematurity in Outborn and Inborn Babies at a Tertiary Eye Care Hospital. Indian Pediatr. 2020 Jun 12

Search PubMed for


Chandra PAggressive Posterior Retinopathy of Prematurity (APROP): A Preventable Challenge.DJO 2020;31:7-8


Chandra PAggressive Posterior Retinopathy of Prematurity (APROP): A Preventable Challenge.DJO [serial online] 2020[cited 2020 Dec 3];31:7-8. Available from: