At the recently held Asia-Pacific Vitreo-retina Society congress (APVRS 2018) in Seoul, Korea, several ophthalmologists shared their experience and pearls of wisdom in managing potentially devastating conditions affecting children in a session called: Pediatric Retina and Retinopathy of Prematurity.
With still developing or as immature organs, children’s eye care and visual needs differ from those of adults. For example, diseases like retinopathy of prematurity (ROP) – which predominantly affects premature infants – pose specific challenges in both examination and treatment. Overcoming these challenges is vital as this common cause of visual loss among children can lead to lifelong vision impairment if left untreated.
ROP risk: What are the factors?
Dr. Sang Jin Kim, M.D., Ph.D., from the University School of Medicine in Seoul, explained that ROP is a very complex disease with a host of risk factors, including prematurity and oxygen treatment. There are maternal risk factors like hypertension, age, medication and smoking; prenatal and perinatal causes like chorioamnionitis, assisted conception and mode of delivery; as well as infant factors like race, ethnicity and gender. In addition, multiple births may also play a role, and there are other contributing influences like anemia, transfusions, thrombocytopenia, sepsis, and nutrition.
“There is also evidence for a genetic basis for susceptibility to ROP,” continued Dr. Kim. “Whole exome sequencing of 100 phenotypically extreme preterm infants revealed several variants with differences in allele frequency between severe and mild, or no ROP.”
This is important as it suggests genetic factors may predispose patients to ROP. Dr. Kim noted several studies that investigated the frequency of specific genetic variants in premature infants with or without ROP. And although no genes reached genome-wide significance, the results revealed genes and pathways that may be important in the development or progression of ROP – which could ultimately aid preventing vision loss and blindness in these cases.
The effect of ROP progression on diagnosis and management
Prompt diagnosis is imperative in all sight-threatening conditions – especially when dealing with children. In addition, keeping a watchful eye on disease progression and managing those changes is vital to patient care.
“Proper screening and timely treatment of severe ROP are essential for successful outcomes,” began Dr. Park Shin Hae from the Catholic University of Korea, Seoul St. Mary’s Hospital.
This is true for ROP – and for important markers of the disease’s severity, like plus disease, which is characterized by severely abnormal dilation and tortuosity of central, posterior retinal blood vessels.* Dr. Park agreed: “It’s also essential to diagnose plus disease in an accurate and timely manner.”
In her presentation, she explained that ROP could be understood as a disease of a continuous spectrum of retinal vascular abnormalities – and identification of vascular progression toward plus disease is critical for proper management.
“A single retinal image may be insufficient to understand how the infant’s eye has been doing,” she cautioned.
Currently, for ROP, wide-angle digital retinal photography is generally utilized – this allows serial comparison of vascular changes over time. “The role of serial montage images is important in the modern management of ROP as they allow direct comparison of retinal vascular progression over time,” explained Dr. Park.
In addition, she says an automated algorithm could be a useful tool to monitor the progression of plus disease in infants undergoing ROP screening: “An incorporation of computer-based image analysis could provide a more consistent and precise identification of retinal vascular progression from serial photographs.”
Looking at outcomes: Anti-VEGF for ROP
According to Dr. Wei-Chi Wu, M.D., Ph.D., from the Chang Gung Memorial Hospital in Linkou, Taiwan, treating ROP with anti-VEGF may have advantageous outcomes.
“One benefit of anti-VEGF for ROP includes a higher success rate for zone-1, or aggressive posterior retinopathy of prematurity (APROP). It [anti-VEGF] is also good for cases with tunica vasculosa lentis (TVL) and unstable systemic conditions,” explained Dr. Wu, noting that while less refractive errors are seen with anti-VEGF, there is also slow retinal vascularization.
However, he notes that the long-term outcome of macular structures following anti-VEGF in ROP eyes remains unclear. Here, Dr. Wu describes a prospective study from January 2014 to June 2016. The study included children aged 4 to 6 with a history of type 1 ROP.
The researchers found that patients treated with intravitreal bevacizumab (IVB) showed greater anterior chamber depth, thinner macular thicknesses and a greater incidence of normal foveal depression than children who underwent laser treatment. In addition, IVB-treated eyes were associated with less myopia and better bare vision than laser-treated eyes.
This led Dr. Wu, along with the researchers, to conclude that “anti-VEGF use for ROP may result in better anatomic and functional outcome if applied judiciously in selected cases.”
Managing surgical complications in ROP
With any surgery, there is always a risk of complications – and patient outcomes depend on the physician’s ability to manage and correct any problems that arise.
For delicate procedures, like vitrectomy for Stage 4 ROP, extra precautions might be taken to avoid or mitigate serious issues. During the session, Dr. Shunji Kusaka, M.D., from the Kindai University Faculty of Medicine in Osaka, Japan, shared his surgical strategy for a successful procedure.
Dr. Kusaka relayed several tips regarding this particular surgery.
This included sparing the lens – or performing lens-sparing vitrectomy (LSV) if possible; releasing traction to the neovascular membrane (NVM); and not being aggressive, or not completely removing the NVM to avoid creating iatrogenic retinal breaks. He also recommended using anti-VEGF if neovascular activity is high for the 2 to 5 days before surgery – this will ensure less bleeding intra- and postoperatively.
“Less is more,” he advised, noting while surgical results for vitrectomy for Stage 4 ROP are relatively good, various complications can occur, including: iatrogenic retinal breaks, breaks in the posterior retina, bleeding and lens damage. “The vitrectomy should be performed carefully and less aggressively.”
“There patients should also be monitored long-term,” he continued. “Even after a successful vitrectomy for ROP, various complications can develop postoperatively, like vitreoretinal complications, myopia, glaucoma and cataract.”
Managing other pediatric conditions: Coats disease
Coats disease was first described by George Coats in 1908. We now know that it presents in five stages, each with increasing severity. Dr. Peiquan Zhao, from Xinhua Hospital at the Shanghai Jiaotong University in China, shared his experience with managing stage 3 Coats disease in China.
In his approach, Dr. Zhao uses a combination of instrumentation and medication, including: external subretinal fluid (SRF) drainage with a 24-G IV catheter; a two-port non-vitrectomy endolaser; anti-VEGF; and pars plana vitrectomy (although this is used less in cases of vitreous hemorrhage, retinal breaks and severe fibrosis, and tractional retinal detachment).
“Using a two-port non-vitrectomy endolaser proved to be thorough and efficient,” he said, noting that the endolaser ablation of normal and aneurysmal vessels was especially efficient in shallow retinal detachment.
He also explained that in Coats disease, the aqueous VEGF level is increased – this can be reduced by laser and anti-VEGF. Dr. Zhao combines anti-VEGF with laser treatment, and has found that together they reduce vascular leakage, exudation and macular edema. “However, do be cautious of the risk of fibrosis after anti-VEGF,” he added.
In an explanation of this procedure, Dr. Zhao detailed results from his study, which comprised 28 eyes of 28 patients with stage 3 Coats disease. The study ran from June 2013 to June 2017, and included 24 males and 4 females, aged 1 to 11. The follow-up period was from eight to 68 months.
Initial treatment included external SRF drainage with a 24-G IV catheter, two-port non-vitrectomy endolaser and anti-VEGF (intravitreal ranibizumab). In this study, no cases received pars plana vitrectomy (PPV) as initial treatment.
Regarding anatomic outcomes, there were no cases that progressed to stage 4 or stage 5 and retina attachment was achieved in 26 cases (or 93 percent). As far as functional outcomes, he said that visual acuity (VA) could be measured in 22 cases.
“Anatomic success can be attained, but it is difficult to improve vision in stage 3 Coats’ disease,” he said.
“This modified treatment − external SRF drainage using 24-G IV catheter, endolaser photocoagulation via non-vitrectomy approach, anti-VEGF treatment − is efficient for stage 3 (exudative total retinal detachment) Coats’ Disease as an initial treatment,” said Dr. Zhao, concluding that further studies are needed in the future.
* Wallace DK, Freedman SF, Hartnett ME, Quinn GE. The Predictive Value of Pre-plus Disease in Retinopathy of Prematurity. Arch Ophthalmol. 2011; 129(5): 591–596.
Editor’s Note: The APVRS 2018 Congress was held in Seoul, Korea, from December 14-16, 2018. Media MICE Pte Ltd, PIE Magazine’s parent company, was the official media partner of APVRS 2018. Reporting for this story also took place at APVRS 2018.
