Pediatric Ophthalmology Conference Highlights Subspeciality Breakthroughs

Not every ocular disease can be identified or managed early in life. But for those that can, it’s crucial that ophthalmologists use all the knowledge at their disposal. The American Association for Pediatric Ophthalmology and Strabismus is particularly focused on those promoting research into those conditions. Held in Scottsdale, Arizona from March 23rd to the 27th, 2022, its 47th annual meeting explored the latest findings from ophthalmic researchers in the areas of emerging neuro-ophthalmic findings, socioeconomic associations with disease and treatment, surgical decision making, as they affect pediatric patients.

These takeaways, culled from 5 studies presented, show the breadth of this research and how, in many instances, the findings from this meeting are not solely the domain of pediatric care, but often extend into general ophthalmology. 

1. Bevacizumab May Be a Future Option for ROP 

Researchers have long seen promise in the ability of anti-vascular endothelial growth factor (VEGF) drugs to manage retinopathy of prematurity; but whether this class of drug can be safely applied to developing bodies, where lack of VEGF may affect neurocognitive development, is another question. A study presented at the AAPOS may offer some insight. 

“I think it’s beginning to build the evidence that it can be safe and effective,” explained Michael X. Repka, MD. Dr Repka, a neuro and pediatric ophthalmology expert who serves as the vice chair for clinical practice at Wilmer Eye Institute, presented numerous studies at the meeting. “Lower doses should help even more,” he said. 

The study the team presented reviewed 2 years of developmental outcomes for patients with retinopathy of prematurity at 2 years of age who were treated with bevacizumab.¹

“Our study examined levels until we started seeing high levels of breakthrough,” he explained. Previously, his team reported intravitreous bevacizumab doses as low as 0.004 mg (<1% of Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity [BEAT-ROP] dose) were effective in treating type 1 ROP. 

They included 120 premature infants (mean patient birth weight was 687 g; mean gestational age was 24.8 weeks) with type 1 ROP in a multi-center, dose de-escalation study. Each patient was treated in 1 eye with either 0.25 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab, while fellow eyes received a dosage 1 level greater than the study eye. Participants (n=49) were assessed using the Bayley developmental scales.

The researchers found correlation coefficients for total dose of bevacizumab to Bayley subscales were -0.19 for cognitive, -0.19 for motor, and -0.14 for language. Of 134 phakic eyes with a cycloplegic refraction, 21 experienced myopia of more than -5.00 D, and 12 infants (17%) had anisometropia (of >1.50 D). They also noted cases of optic nerve atrophy, strabismus, manifest nystagmus and amblyopia.¹

Although the rates of high myopia and ocular abnormalities were comparable to prior research into higher doses of bevacizumab, they did not see a correlation with neurodevelopmental Bayley scores at age 2, the presentation suggested.

2. Silastic Sling Longevity is Not Cause to Delay Ptosis Surgery 

Delaying congenital ptosis surgery after age 3 or 6 months does not yield a sling-survival benefit, according to another study presented at the meeting.² In addition, the report says that “surgical timing for congenital ptosis requiring frontalis suspension should be guided by eyelid height, success of amblyopia management, severity of chin-up head position and anesthesia considerations.” 

Pediatric patients with congenital ptosis and poor levator function are frequently treated first with silastic-sling frontails suspension, according to researchers at the Children’s Hospital of Philadelphia. The team goes on to explain that silastic can be replaced with autogenous fascia lata (AFL) at 4 years of age, when leg length is adequate for harvesting fascia.²

The retrospective cohort study included 391 eyes from 280 children who underwent silastic frontalis-sling surgery (169 unilateral, 111 bilateral) for congenital ptosis before 3 years of age. Patients with mechanical, traumatic, congenital fibrosis of the extraocular muscles (CFEOM), or myasthenia-related ptosis were excluded from the study. Researchers used Kaplan-Meier survival analysis with inter-eye correlation adjustment to compare time to sling failure between early (<6 months, mean: 2, 136 eyes) and delayed (6 to <36 months, mean: 12, 255 eyes) surgery groups. They also performed a secondary analysis of very early surgery (<3 months, 48 eyes).²

The researchers found that 3-year sling-survival estimates were 73% (95% CI 64%-81%) for early surgery and 79% (73%-85%) for delayed surgery (Cox-univariate hazard ratio 0.76 (0.44, 1.32) P =.33). Of the 220 eyes with follow-up to 4 years, survival did not differ (63% early, 68% delayed, P =.47). Likewise, complication rates did not differ (15% early, 10% delayed, P =.16), nor did survival rates following very early (74%) vs later (78%) surgery (P =.88).²

3. PHOMS are a Masquerader Ophthalmologists Need to Know

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) can give the appearance of a swollen disc, and for clinicians who do not have access to enhanced depth imaging optical coherence tomography (EDI-OCT) technology, the finding could raise red flags. It may appear on other modalities as similar to papilledema, which could be indicative of a brain tumor or other serious conditions. However, PHOMS are a benign finding that researchers have only recently begun to distinguish from optic nerve drusen. Neuro-ophthalmologists are currently steeped in research exploring this finding — and it’s not yet clear whether anything can, or should, be done to address it. 

A report presented at the AAPOS highlights the utility of EDI-OCT in observing PHOMS and reveals other details researchers have established after observing 43 participants with bilateral PHOMS (median age 14.2 years, 31 girls, 12 boys) in a 4-year study.³ A total of 24 patients had optic nerve drusen and 16 patients had concomitant papilledema. Of the 33 patients who underwent neuroimaging as part of a papilledema work-up, 20 had neuroimaging prior to being seen at a clinic. Eight had positive neuroimaging signs relating to elevated intracranial pressure (ICP), of which only 3 appeared to have true papilledema.³

While the imaging can help create a more complete picture of the structural integrity of the optic disc and its surrounding area, it is not necessarily something that would require a particular work up protocol, according to Lauren Ditta, MD, an investigator who worked on the study and practices out of Memphis, Tennessee.

“PHOMS have been found with a number of different ocular conditions including papilledema and previous papilledema. In our study, for example, in patients noted to have an elevated intracranial pressures (ICP), after their ICP normalized, the PHOMS shrunk in size. So, you can see them in an acute case of papilledema and you can see them in someone whose papilledema is resolving. They can also be seen in the setting of concomitant drusen which is also something we noted in our patient cohort,” Dr Ditta explained. In fact, more than half of the participants of the study actually had concomitant drusen. “You can see the PHOMS in patients with vein occlusion, anomalous discs, myopia” specifically high myopia, she added. In fact, according to the presentation, PHOMS may be the most common cause for pseudopapilledema in children. And patients with PHOMS are likely to end up in your clinic, as they have for Dr Ditta. 

“We were getting a lot of patients referred in — especially from optometrists — with concern that ‘the nerve is swollen.’ When we teach residents characteristics of a swollen optic nerve, some of the things we talk about looking for are the blurred disc margins or the elevation of the disc, or both, and you can see those exact things in PHOMS. So, the question is ‘when is this concerning enough for me to do a further work up and when is it not?’ That’s where the discussion really gets interesting. In this particular study, we were trying to look to see how many times we needed to do further workups and how many times could symptoms help guide us vs how many times we just observed? A majority of the patients did end up needing further evaluation. And, interestingly, in most of these the work up was done before they came to see us,” she said. “In pediatrics, we’re always trying to figure out the appropriate work up so we don’t miss a diagnosis of papilledema that could be both vision- and life-threatening. But, at the same time, we’re asking ‘when is testing unnecessary?’” PHOMS can add more confusion to that mix, she said. Currently, it neither indicates a further work up is or is not needed for certain. “I think until we can further recognize PHOMS as an isolated entity of benignity, we must remain vigilant and continue monitoring to make sure we’re not missing anything more concerning.”

Although the precise protocol for how to clinically respond to a PHOMS finding has yet to be fully elucidated, one thing is clear. “It offers an explanation to parents that we didn’t have before, rather than just saying the disc looks anomalous or concerning,” she said. Having an understanding of PHOMS — limited though it may be — gives clinicians the ability to explain that “this is something that has been described and that we can follow over time.” Yes, it’s likely one more cause of pseudopapilledema but it’s a useful explanation for patients and their parents. 

4. Social Inequities Can Hamper Amblyopia Treatment Outcomes 

One presentation reviewed the follow up of patients treated for amblyopia and found that visual impairments persist most commonly in 2 groups of patients: patients who are Black, and those on Medicaid.⁴ “These aren’t patients who don’t have access to care,” Dr Repka explained. “These are patients with access to be in the registry. So why are disparities still being seen in these groups? Researchers haven’t said for certain that their study supports any particular hypothesis about this, but the study did find that other racial/ethnic groups and those with commercial health insurance appear to have better outcomes. 

The team looked at the IRIS registry and established that, from a cohort of 18,841 children aged 3 to 7 years who were eligible for IRIS-50, 77.3% were successful. The study also took into account 9762 children aged 8 to 12 years, and found they were 55.5% successful. However, in that first, younger group, the odds ratios for treatment success was significantly lower for patients who were Black (0.71; 95% confidence interval (CI)=0.62 to 0.83) compared with those who were White. Those with Medicaid insurance also had lower success rates than those with other insurances (OR= 0.65; 95% CI = 0.60-0.71), according to the report.⁴

For the older group, the odds ratio for treatment success was also lower in those who were Black (0.81; 95%CI=0.68-0.96) compared with those who were White and Hispanic. In fact, children who were Hispanis had a greater likelihood of success (OR=1.16; 95% CI=1.03-1.31). Again, for this group Medicaid was associated with a lower probability for success (OR=0.84; 95% CI=0.77-0.93).⁴ 

Dr Repka said the next logical step is to ask why researchers are seeing these findings. “Is it biological? We don’t think so. Is it that people don’t pay as much attention to these patients? That would be possible. Is it that they’re not getting the treatments that were prescribed (such as glasses, which are a primary part of the treatment)? That would be possible. We just don’t know yet.” But there are some things that ophthalmologists can do to help combat this inequality in their practices. One would just to be aware of the discrepancy. “A simple thing to do is to teach the importance of cultural barriers,” Dr Repka said, speculating that, perhaps, some of the reasons for these results could be cultural. “My take is: this simply opens eyes to the problem.”

5. Pediatric Patients May Require Mental Health Counseling  

Anyone with a chronic illness — especially one that could threaten perhaps their most valued sense — is likely to experience increased anxiety and, possibly be prone to depression. That may be intuitive, but research does show a quantifiable decline in  quality of life for children with visual impairment.⁵ Research presented at this year’s AAPOS shows that merely having an eye disease, and undergoing the accompanying tests and treatments required to manage it, is associated with mood disorders, increased anxiety, and even bipolar disorders in children and teens. The researchers looked at a range of ocular conditions that included glaucoma, cataracts, congenital optic nerve disease, congenital retinal disease, and blindness or low vision, and found mood disorder associations across the board.

For children, medical treatment is no fun, explained Dr Repka, who was also one of the researchers for this study. He and the other investigators reviewed de-identified commercial insurance claims between January 1, 2007 and December 31, 2018. They included records of 11,832,850 patients younger than 19 years (mean age of 8.04±5.94 years at first claim) and evaluated them for mental illness claims, looking at the association of mental illness and eye disease claims. 

The researchers found a statistically significant association with schizophrenia (OR 1.54, 95% CI: 1.48-1.61, P <.001), anxiety (OR 1.45, 95% CI: 1.43-1.48, P <.001), depression (OR 1.27, 95% CI: 1.25-1.29, P <.001), and bipolar disorder (OR 1.27, 95% CI: 1.21-1.31, P <.001). 

“It’s probably the treatment for a medical condition and the feeling of being disadvantaged” that leads to these findings, Dr Repka suggested. 

Armed with this knowledge, ophthalmologists should report signs of such issues to the patient’s pediatrician for the consideration of a referral to an appropriate therapist. “Parents really rely on pediatricians to manage all facets of their child’s care,” Dr Repka explained. 

Therefore, the onus may be on the pediatric ophthalmologists to be aware of the early signs of these issues, and to educate pediatricians about this connection to eye conditions. “These are messages that will take time to disseminate,” he said. 

The AAPOS is a specialty group, but many of the findings presented at this year’s meeting add crucial details that can help any ophthalmologist understand more about the treatments their care can offer.

References

1. Wallace DK, Hercinovic A, Freedman SF, et al. Two-year ocular and developmental outcomes of a phase 1 dosing study of bevacizumab for retinopathy of prematurity. Paper presented at: The American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, AZ. Paper #13.

2. NaPier EM, Binenbaum G, Yu Y, Ying G-S, Revere KE. Timing of initial frontalis suspension for congenital ptosis. Paper presented at: The American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, AZ. Paper #16.

3. Eshun E, Gwin JC, Moser S, Ditta L. Peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a pediatric population referred for suspected papilledema. Paper presented at: The American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, AZ. Paper #10.

4. Repka MX, Li C, Lum F. Amblyopia treatment outcomes from a clinical data registry. Paper presented at: The American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, AZ. Paper #1.

5. Chadha RK, Subramanian A. The effect of visual impairment on quality of life of children aged 3–16 years. Bri J Ophthalmol. 2011;95(9):642-645. doi:10.1136/bjo.2010.182386

6. Meer EA, Lee YH, Repka MX, et al. Association of mood disorders, substance abuse, and anxiety disorders in children and teens with eye diseases. Paper presented at: The American Association for Pediatric Ophthalmology and Strabismus 2022 Annual Meeting; March 23-27; Scottsdale, AZ. Paper #28.