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Nucci P (ed): Pediatric Cataract.

Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

State of the Art in Pediatric Cataract Surgery Kanwal Ken Nischal Department of Pediatric Ophthalmology and Strabismus, Eye Center, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pa., USA

Abstract

Pediatric cataract surgery has evolved dramatically in the past 10 years. Our understanding of the child’s eye in terms of tissue mechanics, neurobiological plasticity and physiological growth has facilitated better and better surgical outcomes. The fact remains that the younger the child, especially in infants, the more difficult the surgery.

It is also true not only that a child’s eye is not a small adult eye [1] but also that the child him- or herself is not a small adult. The importance of this statement is evident when discussing the effects of anesthesia and fluid input on infants during infant cataract surgery.

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Pediatric cataract surgery has evolved dramatically in the past 10 years. Our understanding of the child’s eye both in terms of tissue mechanics, neurobiological plasticity and physiological growth has allowed better and better surgical outcomes. The fact remains that the younger the child – infants especially – the more difficult the surgery. It is also true to say that not only is a child’s eye not a small adult eye, but also that the child him- or herself is not a small adult. The importance of this statement is evident when we discuss the effects of anesthesia and fluid input in infants during infant cataract surgery. This chapter discusses the factors that should help give a child the best possible outcome after cataract surgery including timing of surgery, type of operation, biometry, the size and type of intraocular lens material , postoperative refraction, operative considerations, wound size and type, capsule management, anterior vitrectomy technique, wound closure and viscoelastic removal and perioperative med© 2016 S. Karger AG, Basel ications.

Fig. 1. A posterior subcapsular cataract in a 3-year-old boy. He was not diabetic, and the cause of the cataract remains unknown.

Timing of Surgery

The timing of surgery is influenced by the age of the child, the severity of lenticular opacity, and its effect on the visual system. A recent individual meta-analysis [2] of over 700 infant cataract surgeries has put beyond doubt the fact that surgery before 4 weeks of age dramatically increases the risk of glaucoma. In unilateral cases, waiting beyond 6 weeks is not recommended, and in bilateral cases, waiting beyond 8 weeks is not desirable, either. In older children, the timing of intervention depends on the severity of lenticular opacity [3]: a lamellar or posterior subcapsular cataract (fig. 1) that allows visual acuity of 20/40 in dim light in the examination lane may cause a drop in visual acuity to 20/70 in sunlight. In such cases, a glare test should be employed, and if visual acuity drops by 2 or more lines, surgery should be considered. In all such cases, the loss of accommodation must be balanced against the gain of central visual acuity in an ambient light setting.

While in adults, the choice of cataract surgery is fairly straightforward, with nuclear phacoemulsification, lens cortex aspiration and intraocular lens (IOL) implantation being the standard procedure, the options of procedures for children include: • Lensectomy • Lens aspiration with IOL implantation • Lens aspiration with primary posterior capsulotomy (PPC) and IOL implantation • Lens aspiration with PPC, anterior vitrectomy (AV) and IOL implantation • Lens aspiration with PPC, AV, IOL implantation and posterior capsular optic capture

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Nucci P (ed): Pediatric Cataract.

Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Which Operation to Choose?

Lensectomy should be performed with a modern automated vitrector, and most of these machines now employ venturi pumps. In children, the vitreous is quite firm, so it is important that the vitrector be set to aspirate and then cut, not the other way around.

If the vitrector is not set up properly, the AV at best may take longer or at worst may not be performed at all. It is worth trying to leave enough capsular support in case a secondary IOL needs to be placed further down the line. Interestingly, work by Walton and colleagues [4, 5] has shown that the cause of open angle glaucoma after infant pediatric cataract surgery may be exposure of the trabecular meshwork to residual lens epithelial cells. When capsule-sparing lensectomy is performed, lens epithelial cell proliferation is inevitable. An adequate AV should be performed to prevent pupil block postoperatively (see below).

Lens aspiration with IOL implantation should be performed in those children in whom posterior capsular opacification is less likely to occur (usually over 8 years old) or in whom yttrium aluminum garnet (YAG) laser capsulotomy can be anticipated to be completed awake (again, usually over 8 years of age). While the child’s age is often the determining factor, in patients with developmental delay or nystagmus, PPC should be considered to avoid the need for YAG capsulotomy or surgical capsulectomy later. There is evidence that leaving the posterior capsule intact in children 6 years of age or under will result in capsular opacification [6]. The likelihood of visual axis opacification is decreased further if an AV is performed in tandem with a posterior capsulotomy, which is usually conducted in children younger than 4 years of age [7]. Reports of an intact anterior hyaloid face and PPC when using hydrophobic acrylic IOLs suggest that visual axis opacification rates are low [8]. To further reduce the incidence of visual axis opacification, posterior capsular optic capture has been advocated [9]. This procedure can be technically difficult in very young children but should be a definite consideration in children over 1 year of age.

Whether primary IOL implantation in infants offers any protective effect against pseudophakic glaucoma is controversial and worthy of a chapter on its own. In this chapter, suffice it to say that IOL implantation should be considered in each individual case and that pertinent considerations should include the anatomy of the eye, the developmental status of child, the presence of other sensory abnormalities, the social situation and the number of siblings. It is also important to stress that primary IOL implantation in children less than 2 years of age may result in further surgical intervention for visual axis opacification. It is unclear at present which technique, lensectomy or lensectomy with primary IOL implantation, is better for children [10, 11].

If an IOL is to be used, then biometry could be done awake if the child is cooperative enough and should be done sufficiently in advance of surgery to allow time to obtain an appropriately powered IOL. In reality, most children need biometry immediately

State of the Art in Pediatric Cataract Surgery

Nucci P (ed): Pediatric Cataract.

Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Biometry

prior to surgery under general anesthesia, necessitating that a large stock of IOLs of varying power be stored on site. Parents should be warned that if an unexpectedly low IOL power is needed, the child may have to be woken without surgery for the appropriate IOL to be obtained, with surgery performed at a later date.

While it is clear that the immersion A scan is more accurate in assessing axial length [12] because the target refraction is often hypermetropic, with the aim that the eye will grow to emmetropia, there is no good evidence in children that the immersion A scan is better than the contact A scan in terms of the final refractive outcome [13].

While there is no one good equation for pediatric biometry [14], the Hoffer Q formula may be used for eyes with a short axial length (less than 20 mm), and the SRK-T formula may be used for eyes with a longer axial length. While a cut-off of less than 20 mm may be used, there is no good published evidence to suggest that one equation is better than another at any particular axial length. However, as far as the Hoffer Q equation is concerned, this lack of evidence may be because the predicted anterior chamber depth (ACD) after surgery supplied by the manufacturers pertains to adults.

If this is used in pediatric cases, the IOL power for a given predicated postoperative refraction is likely to be incorrect. One option used by this author is to measure the ACD and add 1.5 mm to give an estimated ACD. Measuring the corneal curvature under general anesthesia necessitates the use of automated handheld keratometers, and the accuracy of these instruments can vary at times.

The Size of the Intraocular Lens

The capsular bag diameter (crystalline lens diameter + 1 mm) varies with age: 7 mm at birth, 9 mm at 2 years, 9–10 mm at 5 years, 10–10.5 mm at 16 years and 10.5 mm at >21 years [15]. It is important to avoid implanting an IOL that is too large for the size of the capsular bag. In practice, hydrophobic acrylic foldable implants are compressible enough to be placed in smaller capsular bags, but this is not the case for rigid one-piece IOLs. Rigid IOLs with a total diameter of 12.5 mm can be safely placed in 9-mm capsular bags [16]. Parents’ concerns that an IOL may have to be replaced as the child grows are unfounded because once the IOL is placed in the bag, there is very little, if any, capsular growth after lens aspiration [15].

Hydrophobic acrylic IOLs have become the implant of choice for children. Polymethylmethacrylate, either unmodified or heparin surface-modified, has been shown to be associated with more postoperative inflammation than hydrophobic acrylic. Whether

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Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Intraocular Lens Material

this is a direct material effect or is related to the larger wound size needed to implant a rigid IOL is unclear [17].

Lens Power

Ideally, a child should be left as close to emmetropia as possible to allow for maximal visual rehabilitation. However, there is good evidence that the pseudophakic pediatric eye continues to grow like a normal phakic eye after IOL implantation [18–22]. This means that given that eye growth has three phases, a rapid stage in the first 18 months of life with an average growth of 3.75 mm, followed by a slower growth stage until 8 years and then another stage until the late teens, ultimately producing an axial length of 23 mm [23]. This means that the younger the child, the greater the risk that leaving a child emmetropic could result in a high degree of myopia. Leaving an infant emmetropic could result in a myopic shift of 9 diopters by 18 months of age. Based on this assumption, it is recommended to under-correct so that the child is left hypermetropic. Despite this precaution, the myopic shift may be large and be considerably variable [24]. Age is an influencing factor, with younger pseudophakic children exhibiting larger and more unpredictable myopic shifts [24]. However, it is difficult to judge which eyes will develop a significant refractive shift following IOL implantation in infancy, as a child’s pre-operative axial length and postoperative keratometry results, the presence of other ocular disorders, and the power of the implanted IOL poorly correlate with the degree of postoperative shift [24].

A team that includes optometrists and orthoptists is needed for the postoperative monitoring and treatment of amblyopia. The younger the child, the greater the amblyogenic effect of hypermetropia. Therefore, timely spectacle/contact lens correction is mandatory.

It is essential that the surgeon undertaking pediatric cataract surgery be fully aware of the effects of anesthesia on the child’s eye. Again, this issue is more relevant for younger children, although it is also important to help make the operative conditions the best they can be. Laryngeal masks are popular, but their use means that the child will not be paralyzed, and often, if the patient’s eye is not seated deeply enough, the eye will start to roll up. This author feels strongly that the eye should be in a stable position without the use of a traction suture. The reason for this is that if we accept that there is a risk of glaucoma postpediatric cataract surgery, especially in infants, then using a superior rectus suture violates the conjunctiva. Studies have shown that such a violation, especially if there has been bleeding, makes subsequent filtration surgeries more likely to fail [25].

State of the Art in Pediatric Cataract Surgery

Nucci P (ed): Pediatric Cataract.

Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Operative Considerations

Furthermore, in children under 4 years of age, certainly in infants, regarding the risk of iris prolapse when an IOL is to be implanted and the wound is enlarged, the role of the end-tidal partial pressure of CO2 needs to be considered, and whenever possible, the end-tidal partial pressure of CO2 should be 30 or lower [26, 27].

Size and Position of the Wound

The wound can be placed at the limbal cornea or the clear cornea or in the sclera. To avoid violating the conjunctiva, for reasons explained above, the former two choices are preferred. In children, the size of the wound is less of a concern because all wounds in children should be sutured closed. Evidence suggests that the use of 10/0 vicryl reduces the incidence of long-term induced astigmatic changes [28, 29].

Even wounds as small as 20G equivalent should be sutured to prevent aqueous leakage, anterior chamber shallowing, and/or the potential formation of peripheral anterior synechiae associated with secondary glaucoma.

Managing the pediatric capsule is notoriously difficult because of its elasticity. As a consequence, different authors have devised various methods of creating an anterior capsular opening; these methods have included radiofrequency diathermy, vitrectorhexis, plasma blade incision, manual capsulorhexis, two-incision push-pull rhexis (TIPP rhexis) and femtosecond laser incision [30–39].

The currently used techniques for pediatric anterior capsulotomies include vitrectorhexis, manual continuous curvilinear capsulorhexis (CCC), can-opener, and radiofrequency diathermy [30–39]. Other devices, such as the plasma blade, the diacapsutom, and the pulsed electron avalanche knife, have been suggested to minimize zonular tension and prevent peripheral CCC extension but have not become popular.

Elasticity and thickness of the anterior capsule in young children make manual CCC the most difficult technique, with a steep learning curve. It can be performed either with a cystotome or with forceps. Manual CCC has been shown to produce the most extensible capsulotomy and the smoothest edge based on scanning electron microscopy evaluation in a porcine model [40].

Although manual CCC has been the gold standard procedure, some surgeons prefer to use the vitrector for very young patients and manual CCC for older children. In vitrectorhexis, a low aspiration rate and a high cut rate are employed to generate an anterior capsular opening. The vitrector port can be employed face down so that the initial cut is employed to break into the capsule, and then, a smooth circular motion can be employed to complete the opening. Alternatively, after the initial cut is made, the port is turned up, and the opening can be made in exactly the same way; however, the surgeon

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Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Anterior Capsule Management

State of the Art in Pediatric Cataract Surgery

Nucci P (ed): Pediatric Cataract.

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now has a view of where the cut is being made. A venturi pump is best for this technique because a peristaltic pump relies on occlusion of the port to develop aspiration vacuum, which of course is only momentary given how thin the capsule is. The author preferentially uses this technique when no implant is being used. The reason for selecting this method is that there is good evidence that the rhexis edge produced by this method is not as robust as a manual tear [40]. Comparison of mechanized anterior capsulectomy and manual CCC in vitro (18 pairs of postmortem eyes aged 4 days to 16 years) in which one eye of each pair underwent vitrectorhexis and the other eye underwent manual tear resulted in a radial tear in one of 18 eyes (16-year-old eye) treated via vitrectorhexis but none of the eyes treated via a manual tear. However, in 6 eyes (all under 5 years of age), the manual tear could not be successfully continued or completed [41].

The traditional manual capsulorhexis technique is by far the most popular around the world, mainly because individuals who perform surgeries on adult cataracts as well as pediatric cataracts perform the majority of pediatric cataract surgeries worldwide [42].

The transition from the adult capsule to the pediatric capsule has a definite learning curve. Using a capsulotomy needle is possible but is more difficult than using capsulorhexis forceps. The younger the child, the more elastic the capsule and the greater curvature of the anterior lens capsule. To account for these two factors, a heavy viscoelastic substance should be used to hyper-inflate the anterior chamber and thus flatten the anterior capsule as much as possible. In this way, while the capsule may be elastic, the surgeon no longer has to worry about the tear running down the anterior curvature of the lens. The trick is to start in the center of the area in which rhexis is needed and make short tears and re-grasp at the root of the tear to have maximum control. It is best to spiral the tear until the desired size is obtained. Every time the flap is re-grasped, it is important to pull toward the center of the capsule, as the elasticity of the capsule will give the desired curvilinear edge; otherwise, the edge will tend to tear out, and the capsulorhexis will become bigger and bigger. The disadvantage of this technique is that it takes some time to get used to generating a consistently sized capsulorhexis.

The use of trypan blue staining to visualize the capsule when there is completely white lens opacity has been shown to immediately physically reduce the elasticity of the human lens capsule after application. This, in turn, makes the pediatric capsule stiffer and less elastic [43]. The traditional method, manual CCC, has a very steep learning curve in children.

Nischal [35] first described TIPP rhexis in 2002. This technique entails the performance of two stabs using a microvitreoretinal (MVR) blade (fig. 2b) after the anterior chamber has been inflated with a viscoelastic substance. In this technique, it is better to avoid hyper-inflating the eye because the curvature of the anterior lens actually helps to make the rhexis more rounded. This technique differs depending on the age of the child.

In infants, two stabs are made in the anterior capsule, and the distance between these stabs approximates the eventual diameter of the rhexis (fig. 2). A caliper can be

a

d

c

b

e

f

g

placed on the cornea to give the surgeon a guide as to the appropriate site to place the initial stabs (fig. 2a). This author uses an IOL that is 6 mm in diameter, so the eventual diameter of the rhexis needs to be 5 mm. The caliper is set at 4.5 mm, allowing for slight enlargement if needed. The distal edge of the proximal flap is grasped (fig. 2c), and the flap is pushed to the center of the capsule (fig. 2d). Once the tear reaches half the desired distance (fig. 2d), the flap is released, and the proximal edge of the distal flap is grasped and pulled (fig. 2e). At this stage, one of two things will happen: either the tear formed by pulling the distal flap will be the same size as the initial tear, and in such cases, the two tears can be joined slowly to form a complete rhexis (fig. 2f, g); alternatively, the distal tear will be narrower than the initial tear (fig. 3). If this happens, one side of the initial flap is grasped and used to complete the rhexis, making sure to include the initial distal stab in the rhexis.

In older children, after the initial two stabs are made, as the distal flap of the proximal flap is grasped, it may become evident that the tear is going to be too narrow.

Under these circumstances, it is better to adopt a spiral technique, in which the flap is grasped to the left (or right – this is arbitrary) and the flap is pushed slightly outward

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Fig. 2. Composite figure showing the TIPP rhexis. a Calipers are used to give the surgeon an idea about where to place the stabs in the anterior capsule. b An MVR blade is used to make two stab incisions; the distance between the incisions is approximately the diameter of the rhexis to be fashioned. The distal flap of the proximal stab is grasped (c) and then pushed toward the center of the eye, producing a capsular flap (d, blue arrow) and a tear (white arrows). e The proximal flap of the distal stab is next grasped and pulled toward the center of the eye. f, g In young children, the two tears meet, and there is an intact anterior capsulorhexis.

a

b

c

d

and then re-grasped and pulled towards the center of the capsule. This process is repeated until the tear is extended around the distal stab to include it in the tear. This is repeated for the proximal flap of the distal stab (fig. 3).

This experience with this technique was reported in 2006 [36]. The mean age of operation was 70.21 months (range, 4 weeks–18 years). All eyes underwent anterior TIPP rhexis, and 41 eyes specifically underwent posterior TIPP rhexis. While no rhexes were lost during the TIPP technique, 4 anterior capsular tears were reported, 1 of which occurred during irrigation and aspiration and 3 during rigid lens insertion. No late complications were noted. All eyes had anterior rhexis diameters that were smaller than the optic diameter.

Recently, Dick and colleagues [38, 39] have described promising results with femtosecond laser- assisted anterior and posterior capsulotomies in four children. For proper central positioning of the IOL, the anterior capsulotomy should be smaller than the IOL. An ideal diameter of a capsulotomy should be 4–5 mm for an IOL with an optic diameter of 5.5–6 mm. Smaller capsulotomies may result in severe capsular phimosis, as 15% shrinkage of the capsular bag diameter occurs over 6 months [44].

State of the Art in Pediatric Cataract Surgery

Nucci P (ed): Pediatric Cataract.

Dev Ophthalmol. Basel, Karger, 2016, vol 57, pp 15–28 (DOI: 10.1159/000442497)

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Fig. 3. A schematic of how to perform TIPP rhexis. a Two stab incisions are made with an MVR blade. b The distal flap of the proximal stab is then grasped and moved toward the center of the eye. c The proximal flap of the distal stab is subsequently grasped, and the proximal flap is pulled toward the center. d Each flap is then pushed or pulled appropriately to create the rhexis.

Lens Aspiration

Phacoemulsification is very rarely necessary for pediatric lens removal. Lens aspiration is usually sufficient. Using bimanual techniques reduces fluctuations in the anterior chamber and is recommended. Moreover, when the anterior chamber has been inflated with viscoelastic material for capsulorhexis, it is very important to remove the viscoelastic material prior to aspirating the lens material because it is important to avoid impaction of the trabecular meshwork with viscoelastic material.

Unlike in adults, in children, it is important to first aspirate the cortical lens material, especially in white opaque lenses, because this will ensure that if/when the nucleus comes away and there is a posterior capsule defect, most of the lens material will have already been removed. In such cases, if the nucleus is removed first, then the cortical lens material remains and the vitreous normally comes forward; as a consequence, transmitted traction to the vitreous base potentially results in retinal detachment.

Once the lens material is aspirated, it is necessary to polish the capsule, removing as many lens epithelial cells as possible, including both the cells adhering to the anterior capsule and the equator and those adhering to the posterior capsule.

Posterior Capsule Management

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There is good evidence that leaving a posterior capsule intact after cataract surgery on a child under 6 years of age will result in opacification in 100% of cases [6]. The recommendation, therefore, is that a PPC be performed either through the anterior wound prior to IOL placement or after placement of the IOL and closure of the anterior wound. In the latter case, a pars plicata/pars plana approach is applied, and a posterior capsulectomy is performed in this manner in children under the age of 6 years.

This author performs primary posterior capsulorhexis through the limbal corneal wound with AV in all children under the age of 4 years or primary posterior capsulorhexis without AV in all children up to the age of 12 years to avoid the need for YAG capsulotomy.

Posterior capsulorhexis, whether done using the traditional complete tear method or using the TIPP rhexis technique (fig. 4), can be done by making the initial stab and then injecting a viscoelastic substance to expand Berger’s space and therefore avoid violating the vitreous face (fig. 4c). If a vitrectorhexis is to be used, it is helpful to have the cutter facing down relative to the posterior capsule with the cutter off. The capsule is aspirated into the port, and the cutter is then turned on, allowing a capsulotomy to be initiated. Some surgeons stain the posterior capsule with trypan blue to make it more easily discernible [45].

a

b

c

d

Fig. 4. A posterior capsulorhexis. a, b The MVR blade is used to make two stab incisions in the posterior capsule. c, d Viscoelastic material is injected through one of these incisions to expand Berger’s space and to avoid prolapse of the vitreous. As per the anterior rhexis, the proximal stab is grabbed and pushed towards the distal flap. The distal stab is pulled towards the proximal tear just made until the two meet.

Anterior Vitrectomy

An AV is performed by keeping the cutter face up and using a high cut rate (>500 cpm) and a maximum vacuum of 150 mm Hg. It is also important to take the vitreous that is under the intact peripheral posterior capsule by turning the cutter face down and sweeping around the underside of the posterior capsule. The surgeon may have to swap hands to cover the entire circumference of the capsule. A word of caution when removing the instruments: always remove the irrigating hand piece first, followed by the cutter. If this sequence is reversed, the irrigating hand piece may push a hydrated vitreous out as the vitrector is withdrawn. Some authors like to use intraocular triamcinolone to stain the vitreous so that they can tell that no vitreous remains in the anterior chamber after vitrectomy [46].

In order to remove viscoelastic material safely, the main wound should be closed with 2 interrupted 10/0 vicryl sutures. Then, the bimanual irrigation aspiration instruments can be inserted through one paracentesis and through the open part of the main wound. This allows the wounds to be more watertight. If a posterior opening has been

State of the Art in Pediatric Cataract Surgery

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Wound Closure and Removal of Viscoelastic Material

made, then it is very important that the bottle height of the irrigation be at its lowest; otherwise, the IOL can be pushed through the posterior opening into the posterior segment. This author inserts the aspirating port first and then inserts the irrigating port slowly and carefully. If there is a posterior opening, it is important to avoid attempting to remove any viscoelastic material from behind the lens, as this can cause the lens to flip and therefore destabilize the IOL. As stated above, all wounds should be closed in children, and using 10/0 vicryl, there is no need for extra anesthesia to remove the sutures later.

Perioperative Medications

It is important to make sure that any child in whom an intraocular implant has been placed receive adequate periocular steroids. Failing to do so is asking for marked inflammation and anterior membranes [47]. A regimen used by this author includes intracameral preservative-free dexamethasone [48], subconjunctival dexamethasone, and even orbital floor triamcinolone (1 mg/kg). While the evidence supporting that subconjunctival antibiotics prevent endophthalmitis in adults is poor, they are often used in pediatric ophthalmology. Intracameral antibiotics have been used instead, but the formulation is crucial, and this practice is more common in eye hospitals than in children’s hospitals.

If an IOL has been used, especially with a PPC, it is difficult to always remove all of the viscoelastic material. Using a heavy viscoelastic substance will cause an intraocular pressure spike. One approach under these circumstances is to give 4–7 mg/kg acetazolamide intravenously at the end of the operation and then repeat the administration of this dose orally 6 and 12 h later.

One important consideration is simultaneous bilateral cataract surgery. This has been reported on in children [49], and given the recent controversy about possible neurodevelopmental problems with increased anesthesia exposure [50], this may well need to be revisited as an option for surgery in bilateral cases.

References

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5 Michael I, Shmoish M, Walton DS, et al: Interactions between trabecular meshwork cells and lens epithelial cells: a possible mechanism in infantile aphakic glaucoma. Invest Ophthalmol Vis Sci 2008;49:3981– 3987.

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Kanwal Ken Nischal MD, FRCOphth, FAAP Department of Pediatric Ophthalmology and Strabismus Eye Center, Children’s Hospital of Pittsburgh of UPMC 4401 Penn Ave Pittsburgh, PA 15224 (USA) E-Mail nischalkk @ upmc.edu

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