Journal of Pediatric Ophthalmology and Strabismus

Eye to Eye 

The Approach to the Newborn With Bilateral Leukocoria

R. V. Paul Chan, MD; Judith Gurland, MD; Wadih M. Zein, MD; Patrick Derespinis, MD

Abstract

DeRespinis: Today's discussion is on leukocoria in newborns and infants. Every clinician who deals with children will at some point have to either diagnose, refer, or treat a patient with leukocoria. Depending on the cause, timely intervention may assist us in not only preserving vision and possibly the globe, but also even saving a life. The first patient we will discuss is a consultation in a newborn nursery. A full-term male infant has white reflexes in the pupils of both eyes and bilateral lens opacity that indicates bilateral congenital cataracts. What is your approach to the child? Would your approach differ if it was unilateral versus bilateral?

Gurland: I am fortunate to be in an academic center, but not all infants are born in an academic center. So the resources that I have might be different from those of the pediatric ophthalmologist elsewhere. Communication with the neonatologist and other specialists is extremely important. You may be dealing with something that is part of a systemic situation. I would want to evaluate the monocular versus binocular vision and the vision potential. My first step is to talk to the parents and get a detailed history.

DeRespinis: Let's say that you determine that it is a bilateral case. Does your approach differ in terms of the tests that you order?

Gurland: I do have a different approach when it's bilateral versus unilateral. And sometimes what first appears to be a unilateral cataract is really a very small asymmetric bilateral condition. Many of the bilateral cases are inherited and I may consider involving a genetic specialist in the case.

DeRespinis: Dr. Zein, how would you approach this case in terms of tests that you would order if you determine that it is a bilateral disease?

Zein: From a clinical perspective, I would first establish whether the cataract is associated with other anterior segment findings, glaucoma, or posterior segment disease. For example, nystagmus with an iris stump remnant and foveal hypoplasia would favor a diagnosis of congenital aniridia.Second is to determine whether there are any systemic associations. The cataract might be one clue that allows the neonatologist and the genetics team to do appropriate testing and initiate management accordingly. Family history should be documented. Often we note that the patient has a prominent family history with one of the parents having been affected and having had surgical treatment or sometimes in recessive cases older siblings might have had a similar history.I would also want to make sure that this patient does not have any other anterior segment findings. The timing also is important in this case. It's important to establish with the family early on whether this is unilateral or bilateral.

DeRespinis: Do the newer techniques like next generation sequencing have any place in determining cataract origin?

Zein: The list of genes associated with hereditary cataracts is growing, in part due to the wider availability of next generation sequencing (NGS). Genetic testing should not delay clinical management. Where available, NGS can be a valuable tool in understanding the molecular basis of the cataract and can sometimes identify underlying metabolic diseases or systemic associations.

Gurland: I find the family history to be important because it can direct you to ask for specific genetic testing.

Zein: I could not agree more. Directed genetic testing can also be valuable in specific cases.

Gurland: I would start by looking at the parents. An examination with a direct ophthalmoscope (eg, with a Bruckner test) may show that one of the parents has a small cataract that they didn't even know about.

Zein: Yes, doing a quick examination in the…

DeRespinis: Today's discussion is on leukocoria in newborns and infants. Every clinician who deals with children will at some point have to either diagnose, refer, or treat a patient with leukocoria. Depending on the cause, timely intervention may assist us in not only preserving vision and possibly the globe, but also even saving a life. The first patient we will discuss is a consultation in a newborn nursery. A full-term male infant has white reflexes in the pupils of both eyes and bilateral lens opacity that indicates bilateral congenital cataracts. What is your approach to the child? Would your approach differ if it was unilateral versus bilateral?

Gurland: I am fortunate to be in an academic center, but not all infants are born in an academic center. So the resources that I have might be different from those of the pediatric ophthalmologist elsewhere. Communication with the neonatologist and other specialists is extremely important. You may be dealing with something that is part of a systemic situation. I would want to evaluate the monocular versus binocular vision and the vision potential. My first step is to talk to the parents and get a detailed history.

DeRespinis: Let's say that you determine that it is a bilateral case. Does your approach differ in terms of the tests that you order?

Gurland: I do have a different approach when it's bilateral versus unilateral. And sometimes what first appears to be a unilateral cataract is really a very small asymmetric bilateral condition. Many of the bilateral cases are inherited and I may consider involving a genetic specialist in the case.

DeRespinis: Dr. Zein, how would you approach this case in terms of tests that you would order if you determine that it is a bilateral disease?

Zein: From a clinical perspective, I would first establish whether the cataract is associated with other anterior segment findings, glaucoma, or posterior segment disease. For example, nystagmus with an iris stump remnant and foveal hypoplasia would favor a diagnosis of congenital aniridia.Second is to determine whether there are any systemic associations. The cataract might be one clue that allows the neonatologist and the genetics team to do appropriate testing and initiate management accordingly. Family history should be documented. Often we note that the patient has a prominent family history with one of the parents having been affected and having had surgical treatment or sometimes in recessive cases older siblings might have had a similar history.I would also want to make sure that this patient does not have any other anterior segment findings. The timing also is important in this case. It's important to establish with the family early on whether this is unilateral or bilateral.

DeRespinis: Do the newer techniques like next generation sequencing have any place in determining cataract origin?

Zein: The list of genes associated with hereditary cataracts is growing, in part due to the wider availability of next generation sequencing (NGS). Genetic testing should not delay clinical management. Where available, NGS can be a valuable tool in understanding the molecular basis of the cataract and can sometimes identify underlying metabolic diseases or systemic associations.

Gurland: I find the family history to be important because it can direct you to ask for specific genetic testing.

Zein: I could not agree more. Directed genetic testing can also be valuable in specific cases.

Gurland: I would start by looking at the parents. An examination with a direct ophthalmoscope (eg, with a Bruckner test) may show that one of the parents has a small cataract that they didn't even know about.

Zein: Yes, doing a quick examination in the office can be as powerful a tool in our hands as the family history. If one of the parents has a cataract, then you know this is possibly a dominant inheritance pattern. Then you can consider genetic testing.

DeRespinis: I think that these points are all important. If they're bilateral dense cataracts, we obviously have to approach this in a more expeditious manner.

Chan: I have a question for the other panelists. Retinal specialists often encounter cases with dense vitreous hemorrhage, either unilateral or bilateral. Similar to the question about timing for cataract surgery, what is the ideal time for a bilateral versus a unilateral case? Because that's something we have to think about.

Gurland: As early as practically possible when it's safe for the infant.

Zein: I agree. The anesthesia and neonatology teams should also be involved in this decision.

Gurland: I had one case where we dilated an infant in the nursery a couple of times in a row and the infant ended up with intestinal obstruction. I've also had patients who had apnea when we did scleral depression. I think that so much of this depends upon the whole picture.

Chan: But in a situation where the child is healthy and you're trying to prevent amblyopia, what would pediatric ophthalmologists consider to be the best time to perform surgery?

DeRespinis: There are so many factors involved and I think that's what makes cataract treatment and diagnosis so difficult because each practitioner has to determine what needs to be done now before 3 months of age and what can wait until 8 months of age.

Chan: Right.

DeRespinis: I think if you can have a view of the fundus with both eyes having cataracts, that's less detrimental than having a reasonable view of the fundus with only one eye being affected because you're getting equal stimulation. You might intervene earlier with a unilateral case than you might with a bilateral case.

Chan: That has been my impression about the timing in terms of weeks after presentation.

DeRespinis: The next patient is a 4-month-old female infant who is brought to the office for examination because the parents noted a white reflex in the right eye in photographs. On dilated examination, you noticed a slightly elevated 4-disc diameter lesion in the right eye. The borders are not that clear and some retinal hemorrhaging is noted. What is your approach to this patient and what is your differential diagnosis?

Chan: My approach is to obtain a good clinical examination including funduscopy, a thorough family history, and any imaging (eg, fundus photography, ultrasound) that I can do in the office. I have a RetCam in my outpatient office, so we often take pictures. If I think it may be a vascular lesion, I will use fluorescein angiography to see what's happening. Depending on the in-office findings, I will consider escalating to an examination under anesthesia.

DeRespinis: Let's say your suspicion is retinoblastoma. Does that make it more likely in this situation that the child has a non-hereditary form? It looks like it's unilateral.

Chan: At this point, I'm probably going to do an examination under anesthesia to take a really good look and then get a magnetic resonance imaging study.

DeRespinis: In your experience, what is the most likely differential diagnosis in a patient with this presentation? In addition to retinoblastoma, what else could it be?

Chan: I would think about an astrocytoma or a vascular lesion. You should also consider an infectious etiology.

Gurland: Clinicians who do not have access to an academic institution or a retinal specialist could send a picture of the fundus for a remote consultation, instead of relying on verbal descriptions. We can also ask the parents to take photographs so we can send them on to somebody who knows more than we do.

DeRespinis: Technology has certainly helped us in that regard. There are other retinal situations that can actually result in leukocoria. Suppose it wasn't a mass, but that there was a lot of uncertainty about what you were looking at. Obviously, it could be something else. Are there any other diagnoses you would consider if you didn't actually see a mass?

Chan: I would consider whether there is something that's inflammatory or infectious. For a child with bilateral retinal detachment, the decision tree goes along the lines of whether there is detachment secondary to exudation, whether it is rhegmatogenous or has some sort of tractional component. Ultrasonography is always helpful in these cases and fluorescein angiography for assessing any vascular changes. A number of things can cause white lesions or retinal detachments in infants.

Zein: Such as Coats disease.

Chan: Right. That's where the fluorescein angiography is helpful.

DeRespinis: Now that we've discussed some of the retinal possibilities and the actual lenticular possibilities, what do you do with a child who presents with a leukocoria and you determine that it's corneal and it's actually from the anterior segment?

Zein: My first question is whether it is unilateral or bilateral.

DeRespinis: Let's say that the child presents at birth with a unilateral leukocoria that is corneal in origin.

Zein: I would check if the eye shows signs of buphthalmos and is this an indication of underlying glaucoma that is causing this cornea to look white? I want to make sure that the other eye is not involved maybe to a lesser degree. Is there any history of trauma, such as birth trauma or forceps delivery? After that, I would establish whether the anterior segment looks normal and whether there's any indication of dysgenesis in the anterior segment. Other than this corneal leukocoria, the degree that the leukocoria is affecting my ability to examine structures behind the cornea is also something that I would want to factor in. Can I have a good view posteriorly? Which areas of the cornea are involved is also important.

DeRespinis: Obviously, if it is corneal edema, our differential diagnosis would be different from it being just an isolated lesion. Now that we've determined it's corneal edema, what is your differential diagnosis at this point?

Zein: With unilateral disease, I would like to first establish that this is not asymmetric. Most corneal edema or clouding at this age would typically present as bilateral disease. The possibility of increased intraocular pressure is foremost once I've established that there is corneal edema or clouding in this eye. This could be an anterior segment dysgenesis causing increased pressure in this eye with the other eye being less severely involved. Is there any history of a foreign body that might have caused an infection in that eye? In an infant, one should also consider congenital hereditary endothelial dystrophy in the differential diagnosis.

DeRespinis: So this could be a bilateral case that is so asymmetric that only one eye presents initially with edema, but we also have to consider that the other eye is also involved.

Zein: Yes.

DeRespinis: There was a child who presented with bilateral retinal detachment. We initially thought this patient had cataract, but it turned out that he had lenticular involvement from the actual detachment touching the lens. Dr. Chan, have you encountered this situation in the past?

Chan: We see this not infrequently in my practice and it can be misleading. My approach to this patient would not be dissimilar from what we talked about earlier in terms of the history and diagnostic imaging. If you don't have the equipment to manage this condition, it's going to be important to refer this patient to a center that does have the ability to evaluate it more thoroughly with the different tools that we need. We've ruled out retinoblastoma and exudative, rhegmatogenous, or tractional causes. We previously described a condition in infants who were full term or close to full term who had aggressive posterior vitreoretinopathy, which is really along the familial exudative vitreoretinopathy spectrum, and this is a possibility here.

Gurland: Another condition to consider in the differential diagnosis is non-accidental trauma. I imagine many of us have seen other intraocular pathology, such as retinal detachments, that have occurred after non-accidental trauma. Awareness of this has been raised nowadays, but many of us don't think about it because an infant may not have other systemic findings by the time cataracts develop and the infant presents for examination.

Zein: And in a male infant, x-linked retinoschisis should be considered.

DeRespinis: Along with the diagnosis of Norrie's disease. Yes, there are so many different possibilities in terms of what could cause leukocoria. I think we have to approach it from the actual location, where it starts in the cornea going all of the way back to the retina. This is a daunting topic because of how many different things can cause leukocoria in such a small organ. I think that's what makes this topic so interesting.

Chan: I have an additional comment from the retina perspective. It's so important to do a really good examination so that we don't operate on a child who might have retinoblastoma. Good documentation is also important. If you have bilateral cataracts that are really dense or even a unilateral cataract and you do an ultrasound and you don't see anything going on, make sure you're documenting appropriately. I also recommend a dilated funduscopic examination immediately after that opacity is cleared, even in the operating room while the child is under anesthesia. The reason for this is because even though you don't see anything on ultrasound, there could be posterior involvement or retinal changes that can limit the vision. This is important to document and can explain why a child may have limited visual potential.

DeRespinis: For bilateral dense cataracts where the ultrasound seems normal, should you consider computed tomography or magnetic resonance imaging just to make sure that nothing was missed? I don't know if that's necessary, but, as you said, it's disconcerting to find out later that there was something that you might have been able to see if you did another type of study.

Zein: I think the answer really lies in the situation at the time. The neonatologist or geneticist can also have valuable input. In a patient with congenital cataract who is in the neonatal intensive care unit, I think additional findings would be important. Some of these findings go back to what we've discussed, such as a full eye examination and a full medical and family history, and we're going to leave the possibilities with the family. Having done all of that and not noting additional findings, just having bilateral dense cataracts would not necessarily cause me to order imaging.

Gurland: We should also remember the role of other specialists, such as vision rehabilitation. It's important to maximize potential vision, even if it's something like telling the parents not to put the crib near the window or use red lights instead of full spectrum lights so that you can maximize the child's functionality. It seems logical to us that she had photophobia from corneal or retinal issues, but a lot of parents will think the child just needs more light. Communication is key.

DeRespinis: I would like to thank the panel for participating in this session and adding to our understanding of leukocoria.

This Eye to Eye session was conducted on July 23, 2019.

Authors

R. V. Paul Chan, MD, is from the Pediatric Retina and ROP Service at the Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois.

Judith Gurland, MD, is from the Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, Bronx Lebanon Hospital Center/Bronx Healthcare Network, Bronx, New York.

Wadih M. Zein, MD, is from the Ophthalmic Genetics and Visual Function Branch at the National Eye Institute, Bethesda, Maryland.

Moderator: Patrick DeRespinis, MD

The authors have no financial or proprietary interest in the materials presented herein.

10.3928/01913913-20190919-01

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