The Effect of the COVID-19 Pandemic on Babies and Other Updates in ROP

Retinopathy of prematurity (ROP) is a potentially blinding eye disorder that primarily affects preterm babies. It can result in retinal detachment, myopia, strabismus, amblyopia and glaucoma.

The smaller a baby is at birth, the more likely that baby will develop ROP.
This disorder — which usually develops in both eyes — is one of the most common causes of visual loss in childhood and can lead to lifelong vision impairment and blindness.

By 2020, ROP will be the single largest cause of needless blindness. Delegates heard how the COVID-19 pandemic took a toll on the management and screening of babies with ROP during a session held on the second day of the 5th meeting of the ASEAN Ophthalmology Society (AOS Virtual 2022) on Sunday March 26, 2022.

What India and the Philippines Have in Common

Dr. Rachelle Anzures, of the Anzures Eye, Ear, Nose and Throat Specialty Clinic (Philippines), shared the ways in which clinics adapted to the new norm. “The COVID-19 pandemic has led to the significant disruption of the delivery of health care, including retinopathy of prematurity,” she said. Published reports from the Boston Children’s Hospital (USA), have shown that more infants required ROP examination in 2020 compared to 2019, but fewer examinations were performed. There was an 18% increase in the number of infants screened but there was a 19% decrease in the number of examinations performed.

In India, there was a significant decrease in the number of infants screened and treated in 2020 compared to the previous year. At the All India Institute of Medical Sciences (AIIMS), there was a 73-89% decrease in the number of infants screened and a 63-88% decrease in the number of infants treated. At the Ospital Ng Makati (Philippines), the number of screenings dropped from 79 in 2019 to 30 in 2020. This rose to 50 in 2021. The number of babies treated also fell from 8 in 2019 to 3 in 2020. This rose to 8 in 2021.

Pandemic-related ROP Blindness

During the pandemic, there was an increased incidence of ROP blindness. Because of COVID-19 restrictions, lack of public transport and travel restrictions — not to mention the fear of virus among parents — delayed presentation to ophthalmologists, who were already in short supply. Ophthalmologists have also had to adapt their practice patterns to ensure continued delivery of care without compromising the safety of patients. Infants and toddlers can be asymptomatic carriers or in the pre-symptomatic period of transmission. Implementing source control measures like face masks and social distancing in this age group is difficult, Dr. Anzures noted.

Crying increases the risk of aerosol generation and transmission. Proximity of these patients to caregivers, along with sustained crying, might further increase the risk and load of aerosol. Risk mitigation and infection control measures include wearing proper personal protective equipment, daily screening of staff, proper disinfection of indirect ophthalmoscope and screening instruments, as well as visitor screening prior to hospital entry. Face-to-face interactions are minimized and family counseling is done via teleconference. Disinfection is carried out in between examinations.

While the pandemic has presented many challenges, it has also led to opportunities such as improvements in virtual communications with parents, virtual meetings and lectures. “From an infection control point of view, the pandemic has exposed what we lacked in taking care of our patients. However, it has also accelerated the development of technologies needed to address the problems,” emphasized Dr. Anzures. Advances in telemedicine and artificial intelligence (AI) are seen as being able to bridge the gap in the availability of medical care.

Laser or Anti-VEGF? That is the Question…

While laser remains an important management option for ROP, the use of anti-VEGF may have higher treatment success, better structural outcomes, involve less surgical intervention and less myopia, said Dr. Gavin Tan, senior consultant in surgical retina at the Singapore National Eye Centre (SNEC).

In the RAINBOW study, infants treated with ranibizumab 0.2 mg were twice as likely to achieve clinically-relevant treatment success compared with those treated with laser. RAINBOW was a randomized, multicenter, open-label, parallel-group clinical trial to compare ranibizumab with laser therapy in premature infants with ROP. The primary objective was to demonstrate superior efficacy of ranibizumab 0.2 mg to laser as measured by treatment success at week 24.

The study results showed that a treatment success rate of 80% was achieved with ranibizumab 0.2 mg versus 66% with laser. Ranibizumab 0.2 mg was well tolerated in patients with ROP and the safety profile was as expected in a preterm population. RAINBOW was the first study to report pharmacokinetic and systemic VEGF data in ROP.

A 5-year extension study is currently ongoing, with results expected in 2022. The use of anti-VEGF must however be balanced with the risk of recurrences which may occur later and require a higher follow-up burden, Dr. Tan cautioned. Screening remains the most critical tool to prevent blindness. If ROP is not detected early, this decreases the chances of treating and preventing blindness. “Always involve parents in the discussion,” he added.

The Role of FFA in ROP Pathogenesis

Fundus fluorescein angiography (FFA) could play a central role in better understanding the pathogenesis of ROP, said Dr. Sumalin Trichaiyaporn, a pediatric retina specialist from Queen Sirikit National Institute of Child Health, Thailand.

ROP is a vasoproliferative disorder that can lead to significant blindness in children. FFA is the gold standard technique to study retinal vasculature and a valuable tool for evaluation of the chorioretinal vasculature in vasoproliferative disorders. It appears to be safe in children including neonates with ROP, with no adverse effects reported. Ultra-widefield multimodal imaging, including FFA, has an increasing role in the pediatric retina for diagnosis, treatment and follow-up. The use of FFA is suggested because certain components of the International Classification of Retinopathy of Prematurity (ICROP) are subjective and open to interpretation.

The introduction of anti-VEGF therapy has presented new challenges associated with the recognition of clinical features characteristic of post-treatment regression and reactivation. The pattern of ROP in regions of the world with limited resources is also not adequately described by the current classification system. FFA in ROP is useful to evaluate the position and extent of pathologic vascular proliferation (especially stage 3 disease), the activity of fibrovascular proliferation, the vascular pattern of the retina, the capillary network of the retina, and the extent of photocoagulation.

In conclusion, the supplementation of color fundus photographs with FFA may improve the accuracy for certain classifications and management of ROP. In the era of multimodal imaging, FFA is playing an emerging role in guiding the management of ROP in the anti-VEGF era. FFA may have a role in characterizing vascular maturation after intravitreal anti-VEGF therapy. Prospective multicenter studies assessing the long-term role of FA in this population are warranted, said Dr. Trichaiyaporn.

Editor’s Note: The 5th AOS Congress was held virtually on March 26-27, 2022. Reporting for this story took place during the event.

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