Current management of infantile cataracts

Abstract

Infantile cataracts remain one of the most treatable causes of lifelong visual impairment. While the chance of improving vision for children with infantile cataracts has never been better, significant global and socioeconomic disparities still exist in their early management. Recent epidemiological studies reveal a stable prevalence of infantile cataracts in high-income countries and highlight challenges in determining the prevalence of infantile cataracts in low-income countries. Detailed descriptions of cataract morphology may inform us as to etiology, provide guidance with regards to surgical approach, and have prognostic value. Molecular genetics is providing new insights into the hereditary bases and potential systemic associations of infantile cataracts. For visually significant infantile cataracts requiring surgery to clear the visual axis, surgical techniques continue to evolve based on the experiences and research efforts of skilled teams worldwide. The most common complications of cataract surgery performed in infancy are visual axis opacification and, in about a third of patients, the long-term development of glaucoma. Children with unilateral cataracts generally see well given the presence of a healthy fellow eye. Better visual outcomes in operated eyes, however, are achieved in the setting of early presentation, bilateral infantile cataracts, absence of nystagmus or strabismus, and consistent amblyopia therapy. While intraocular lenses for infants less than 6 months can result in good visual outcomes, contact lenses may be preferred in situations in which they are available and practical. Many studies have demonstrated the benefits of early surgery for infantile cataract. We must strive for the continued evolution of technologies and strategies that have the potential to further improve these outcomes.

1. Introduction

Infantile cataracts are an uncommon, but serious, condition. Compared with later-onset cataracts, infantile cataracts are the most amblyogenic. Not only do most infantile cataracts lessen vision by blurring the retinal image, they also disrupt visual processing pathways of the central nervous system, thereby diminishing lifelong visual potential. Timely surgical intervention and appropriate follow up for optical rehabilitation and amblyopia therapy can mitigate vision loss from infantile cataract. Because the exact age of onset of childhood cataracts may not always be known, congenital cataract, or cataract present at time of birth, will be considered a subset of infantile cataract, defined here as cataract found within the first 12 months of life. This article will focus on the management of infantile cataracts for children undergoing cataract surgery during the first year of life and contributions to this field over the past decade.

2. Public health significance

2.1. Decreased quality of life for children with infantile cataracts

While infantile cataracts are rare, they cause the significant morbidity and mortality associated with early-onset visual impairment.^1,2 When infantile cataracts are identified within the first weeks of life and managed appropriately, the visual prognosis can be excellent, but for those children whose cataracts remain undetected and treatment is delayed, particularly in bilateral cases, the impact of childhood blindness may be profound. Even in situations in which surgery is performed in a timely fashion and perioperative management is rigorously controlled, vision loss from amblyopia remains a significant problem. Children with vision loss or blindness due to infantile cataract have many more years to live without vision than those with adult-onset vision loss.^2,3 Reduced vision due to congenital cataracts decreases quality of life and creates a significant socioeconomic burden.² Quality of life scores for children with congenital cataract living in the United Kingdom obtained using the PedsQL 4.0 instrument were equivalent to those of children with severe systemic diseases.⁴ In many places, children with congenital cataracts may not be able to access mainstream schools or enter the workforce.⁵

2.2. Costs

In addition to the individual, familial, and societal costs of infantile cataracts, the costs of managing these cataracts are also significant. Specialized facilities and equipment, as well as a team of pediatric consultants trained to evaluate, manage, and follow these children over time are essential to provide optical rehabilitation, amblyopia therapy, and prompt recognition and management of any associated vision-threatening problems such as glaucoma. In 2009, the costs of congenital cataract surgery and postoperative care for an uncomplicated case in the United States based on a third payer perspective and using 2008 CPT codes were estimated to be between $15,079 and $27,041 USD per patient.⁶ At 5 years in the Infant Aphakia Treatment Study (IATS) in the United States, the 5-year cost of providing pediatric cataract surgery was calculated to be $27,090 or $25,331, depending on whether an intraocular lens or contact lens was used.⁷ Costing studies of pediatric cataract surgery have also been performed in Maharasthra, India, and in Sub-Saharan Africa that have highlighted the cost-intensive nature of surgery and perioperative care for infantile cataract.^8,9 Gogate and coworkers concluded that pediatric ophthalmologists should make decisions regarding the most cost effective standards of care to rationalize consumable cost.⁸ While several studies have focused on calculating the direct costs of pediatric cataract surgery,^6–10 the indirect costs to the families of these patients are likely much higher in terms of days of work missed to attend doctors’ appointments and to care for a young child postoperatively.

2.3. Progress: neonatal screening and national registries

Improved visual outcomes in many cases of early detection, combined with the high cost of delayed detection of infantile cataracts, underscore the importance of early screening for the problem. In many developed countries, red reflex screening in newborns and young children is routine. One 2013 study in Sweden utilizing a national Pediatric Cataract Registry (PECARE) showed that after a routine screening protocol was instituted in maternity wards and well-baby clinics, congenital cataracts were detected by 6 weeks of age in 75% of cases, resulting in earlier referrals and surgeries.¹¹ When newborn screening protocols in Denmark, that involved a pen-light exam only, and in Sweden, where there was mandated red reflex testing, were compared over the same 5 year period, there was a statistically higher percentage of earlier detection once red reflex screening was instituted in Denmark.¹² Pediatricians play a critical role in detecting infantile cataracts,¹³ and the American Academy of Pediatrics advises red reflex assessment as part of the neonatal and subsequent pediatric eye examinations.¹⁴

2.4. Barriers

Elimination of avoidable causes of childhood blindness such as cataract was prioritized by the World Health Organization and the International Agency for the Prevention of Blindness as part of the VISION 2020 initiative.¹⁵ Challenges persist in all regions of the world with awareness of congenital cataract, delayed diagnosis, late presentation for surgery, access to quality care, and inadequate follow up.^16–31 Parents may not be aware that infants can have cataracts, that their child has a cataract, or that the vision of an infant with a cataract can be improved. Families may not have access to pediatric eye care services or might not be aware such services exist, how to access them, or have transportation to a facility that provides them. Parental fear and anxiety, concerns about cost, and competition for scarce resources within a family may result in delayed diagnosis and late presentation for surgery.¹⁵

Detection of infantile cataract is often delayed in developing countries. For example, in southwest Nigeria in 2011–2015, the median age at presentation for patients with congenital cataract was 18 months.³²At one site in China in 2011, 41% of children presenting with bilateral, and 12% of those with unilateral, cataracts were under 6 months of age, and among these children, 16% with bilateral cataract and 1% with unilateral cataract underwent surgery between 3 and 6 months of age.¹⁶ Average age at surgery of 1314 patients with congenital cataract identified in a retrospective 2014 study from Zhongshan Ophthalmic Center in China was 28 months.³³ Mean age at presentation was 6.9 years for congenital cataract in Madagascar in 2014, with 84% of children lost to follow up 5 weeks after surgery.¹⁷ In Guatemala in 2011, mean age at diagnosis of congenital cataract was 34.9 months, with treatment not pursued in 71% of these cases.²⁹ In India, a 2018 prospective multicenter study found that mean age at surgery for ‘congenital’ cataract was 4 years.³⁴ Furthermore, in multiple settings, gender inequalities in children receiving services for congenital cataract have been noted, with the number of boys exceeding the number of girls receiving care.³⁵ Recognition of this disparity has resulted in declaration of the expectation that “equal and fair medical care be provided to all children regardless of gender.”³⁶

With regards to receiving care, there are shortages of qualified pediatric eye care professionals and few opportunities for pediatric ophthalmology subspecialty training in many regions of the world.¹⁵ In lower-income countries, many infants with cataracts must receive care from general ophthalmologists as this may be the only available opportunity for eye care.¹⁵ Pediatric eye care services in many countries are still non-existent or fragmented. Funding such programs presents a challenge in terms of the facilities, equipment, human resources, and time-intensity required to care for these children, and there is a scarcity of supplies and expertise needed for the postoperative optical rehabilitation and amblyopia treatment of aphakic infants.¹⁵ Some of the barriers that affect initial access to care may also influence the ability of families to obtain follow up care for infantile cataract. In one study in Tanzania, poor follow up was predicted by long distance to a surgical facility, female gender, and poor preoperative vision.¹⁸ In the same study, some parents did not think follow up was necessary when the patient’s vision was improved after surgery.¹⁸ Chougule and coworkers found a logarithmic curve of loss to follow up after pediatric cataract surgery in 169 patients in South India.³⁷

Global efforts are underway to overcome these common and unique barriers to children receiving care for infantile cataracts by means of improving diagnosis, education, access, quality of care and follow up.^{1,8,22,25,28,38,39} Efforts to increase the timely diagnosis of infantile cataracts have included calls for instituting red reflex screening protocols in nurseries and other early childcare settings.^36,40–44 There are also the newer investigation of infrared-reflex assessment with a prototype imaging device to improve diagnostic accuracy, particularly in non-Caucasian children⁴⁵, and the use of community key informants to identify children with eye problems.^46–49 There is increased recognition of the need for public education about the problem of infantile cataract and the need to educate the medical community about the importance of early referrals.

Evidence indicates that quality communication between physicians and patients influences patients’ future therapy and contributes significantly to achieving better outcomes.⁵⁰ There is also increasing recognition that limited literacy is associated with suboptimal patient care and outcomes.⁵¹ Various strategies to enhance physician communication skills have been reviewed.⁵² Since awareness has grown about the shortcomings of traditional, time-of-service education with regards to knowledge retention, attention is shifting to the use of active learning strategies. Chen and coworkers in China in 2020 performed a prospective study randomizing parents of 177 children with congenital cataracts into a multifaceted, interactive health education program versus conventional follow up and found that the interventions (a module and a workshop incorporating technology-based activities, written documents, and online chat group activities to promote participants’ understanding of congenital cataracts) improved parental understanding of their child’s condition and parental satisfaction.⁵³

There is great heterogeneity in pediatric eye care systems, even in the same region of the world. Efforts to improve access to quality care in Sub-Saharan Africa have included concentration of pediatric eye care services into Child Eye Health Tertiary Facilities.²⁶ Many facilities in low-income countries are not equipped to provide general anesthesia to the youngest patients, however, and supplies and equipment problems limit capacity to address the problem of infantile cataract. Furthermore, owing to limited availability of contact lenses in many parts of the world, intraocular lenses are implanted in even the youngest infants out of necessity.

Measures to improve follow up in Sub-Saharan Africa have included telephone calls, patient tracking, parental counseling, and transportation reimbursement.¹⁸ The COVID pandemic has piqued interest in the role telemedicine may be able to play in assisting ophthalmologists and other healthcare workers in diagnosing pediatric cataract and facilitating timely referral.^54,55 International exchanges in human resource development for pediatric ophthalmology and efforts to expand and update curricula for pediatric ophthalmology training are ongoing (http://www.icoph.org; https://cybersight.org).

3. Epidemiology

3.1. Prevalence

The overall prevalence of congenital cataract obtained through a 2016 systematic review of relevant studies conducted world-wide was 0.63–9.74 (median 1.71) per 10,000 children, but the authors found a relative dearth of studies from low and lower-middle income countries, a lack of standardization with regards to case definition and ascertainment methods, and small sample sizes.⁵⁶ Another meta-analysis conducted the same year found the global prevalence of congenital cataract to be between 2.2/10,000 and 13.6/10,000 with an overall pooled prevalence of 4.24/10,000.⁵⁷ Analysis of a 5-year birth cohort (2011–2015) using data from 30 population-based birth defects surveillance programs in the United States generated an overall prevalence estimate of 1.5 (95% CI: 1.4–1.6) per 10,000 live births for congenital cataract.⁵⁸ The incidence of congenital cataract surgery in the first year of life in France 2010–2012 was found to be 2.15/ 10,000 births.⁵⁹ About thirty percent of these children had bilateral surgery.⁵⁹ The PECARE collected basic epidemiological data regarding surgically treated cataract in childhood in Sweden and Denmark between 2007 and 2013 and reported that 266 (46%) of a total 564 operations in children under 8 years were performed before the age of 1 year, with 193 (34%) of these surgeries performed during the first 3 months of life.⁶⁰ In Tuzla Canton, Bosnia and Herzegovina, the estimated incidence of congenital cataract is 2.62 per 10,000 births.⁶¹ Studies have reported an increased prevalence of congenital cataracts in areas of higher rubella burden such as Vietnam and the Philippines.^62,63 In some developing countries, pediatric cataract is the leading cause of surgically treatable blindness, with a 1997 estimate of 200,000 children blind worldwide from bilateral cataract.^64,65 Notably, pediatric cataract has surpassed corneal pathology as the leading cause of avoidable vision loss in parts of Africa.^1,39,65,66

3.2. Risk factors

Infantile cataracts can be hereditary, associated with an ocular or systemic syndrome, or secondary to metabolic disease or intrauterine infections, but most unilateral infantile cataracts and about 25% of bilateral infantile cataracts are idiopathic.^{67–70,71,72} A 2018 analysis of population-based birth defects data with a focus on eye and ear defects in the United States from 2011 to 2015 revealed that congenital cataracts were more frequent among infants of older (40+ years) mothers, while the prevalence of congenital cataract varied little by maternal race/ ethnicity, infant sex, or case ascertainment methodology.⁵⁸ An earlier 2010 study assessed risk factors for infantile cataracts using a case-control study from the National Birth Defects Prevention Study, 2000–2004.⁶⁷ A multivariate analysis was performed to explore associations for risk factors for bilateral and unilateral infantile cataracts of unknown etiology.⁶⁷ The authors found that very low birth weight is associated with both bilateral and unilateral infantile cataracts. Low birth weight is associated with bilateral cataracts and the study suggested an association between primigravidity and unilateral cataracts.⁶⁷ Overall, the findings of the study suggested different risk factors for unilateral and bilateral infantile cataracts.⁶⁷ These findings are supported by the previous work of Haargaard and coworkers in Denmark who investigated risk factors (maternal, demographic, pre- and peri-natal) for idiopathic infantile cataract in 1027 cases/2.9 million children and found no environmental influences associated with infantile cataract (birth order, month/place of birth, cigarette smoking during pregnancy), but did find that low birth-weight children (<2000 g) had a 10.6 fold increased risk of bilateral, but not unilateral, infantile cataract.⁷³

4. Morphology

Infantile cataracts can be unilateral or bilateral, partial or total, with different phenotypes reflecting the timing and the nature of the cause.⁷⁴ Careful attention to the distinguishing features of the various types of infantile cataracts can clarify time of onset and etiology, help guide further ocular and systemic evaluation and management, and even indicate prognosis.^74–77 Some of the most common types of infantile cataracts are anterior polar, fetal nuclear, cortical, persistent fetal vasculature, posterior polar, posterior lentiglobus, and total, but there are other, less common types as well. Specific genetic mutations have been identified in association with certain clinical phenotypes of congenital and early-onset cataracts.⁷⁸

Viewing infantile cataracts through a surgical microscope and review of surgical video can allow for recognition of lens layer involvement that cannot be appreciated on clinical evaluation.⁷⁶ One such review and analysis of surgeries done for unilateral congenital cataract led to the determination that the posterior capsule is more often involved in monocular congenital cataracts than previously thought.⁷⁶ Furthermore, a subsequent study comparing surgical review of unilateral and bilateral infantile cataracts found a much lower incidence of posterior capsular plaque in the setting of bilateral congenital cataracts versus unilateral cataracts. This supports the idea that most unilateral congenital cataracts arise from persistent fetal vasculature.⁷⁹

4.1. Anterior polar

Anterior polar cataract generally consists of a central, 1 mm anterior lens capsule opacity (Fig. 1). This type of cataract is thought to be a remnant of the tunica vasculosa lentis. Anterior polar cataracts may be unilateral or bilateral. While most remain stable over time and do not require surgery, progression of the lens opacity is possible so careful monitoring is required. Furthermore, although this type of cataract does not usually cause visual deprivation necessitating surgery, anterior polar cataract can be a highly amblyogenic condition due to associated refractive error.⁸⁰ Young patients may develop refractive amblyopia from hypermetropic anisometropia and astigmatism without appropriate optical correction and ongoing management.⁸⁰ An eye with unilateral anterior polar cataract may also have shorter axial length compared with the fellow eye.⁸⁰

Fig. 1 –

Anterior polar cataract.

4.2. Fetal nuclear

Fetal nuclear cataracts (Fig. 2) involve varying levels of opacification of the central embryonic and/ or fetal lens nuclei⁸¹ and can progress over time. They are usually about 3 mm in diameter, but the lens abnormalities may extend more peripherally. Especially in unilateral cases, this type of cataract may be associated with microcornea, and these eyes are at risk for glaucoma following cataract surgery.⁷⁷

Fig. 2 –

Fetal nuclear congenital cataracts in 2 patients.

4.3. Cortical lamellar

Cortical lamellar cataracts involve opacification of an ovoid layer of lens cortex between adjacent clear lamellae, or lens opacification located within the lens cortex peripheral to the Y-sutures with central nuclear sparing.⁷⁶

4.4. Persistent fetal vasculature

Failure of regression of fetal hyaloid vessels supplying the developing lens in utero results in the congenital lens opacity known as persistent fetal vasculature (PFV).⁸² Although typically unilateral, the condition can be bilateral in about 15% of patients.^83,84,85 Most cases are sporadic, although genetic inheritance has been described, and PFV may be associated with systemic disorders.^83,86 This type of cataract can vary significantly in terms of size and degree of anterior and posterior involvement but generally consists of a vascularized, retrolental membrane adherent to the posterior capsule (Fig. 3). The membrane extends from the optic disc to the posterior lens surface and is seen on echogram as a thin membrane of low reflectivity. Longitudinal views and high gain enable visualization on B-scan ultrasonography (Fig. 4).

Fig. 3 –

Persistent fetal vasculature.

Fig. 4 –

Longitudinal view on preoperative B-scan ultrasound reveals persistence of hyaloid stalk.

While a full discussion of persistent fetal vasculature is beyond the scope of this article, PFV is associated with the risk of severe ocular complications and resulting decreased vision.⁸³ It is important to detect a persistent hyaloid stalk prior to surgery as severing the stalk during surgery may result in significant hemorrhage. The posterior membranous plaque may also be attached to the ciliary processes (Fig. 5), and there is a high incidence of associated peripheral retinal anomalies.⁸⁷ In cases of PFV, the peripheral retina may extend anteriorly beyond the ora serrata and be incorporated into the fibrovascular plaque.⁸⁷ The affected eye is usually smaller than the fellow eye (Fig. 6) and is at high risk for glaucoma.⁷⁷

Fig. 5 –

Posterior plaque of persistent fetal vasculature with elongated ciliary processes.

Fig. 6 –

Microphthalmos of the left eye in a patient with persistent fetal vasculature of the left eye.

4.5. Posterior polar

Posterior polar cataract, also sometimes referred to as an isolated posterior capsule plaque, involves posterior capsular opacification without an overlying opacity in the cortex or nucleus.⁷⁶ This type of cataract can occur in conjunction with other types of cataract and often can only be appreciated during active lens aspiration as other layers of lens opacification are removed.⁷⁶ These posterior capsular plaques can be very adherent to the internal surface of the posterior lens capsule. Immunohistochemical analysis of the vitreolenticular interface has been performed in several patients with congenital unilateral posterior cataract.⁸⁸ While the presence of collagen type IV was confirmed in posterior capsule samples from both cases and controls, the abnormal presence of collagen type II on the outer surface of the posterior lens capsule was detected only in the samples of cataract patients. This may be indicative of an abnormality of the vitreoretinal interface in these patients.⁸⁸

The clinical appearance of posterior capsular involvement should put surgeons on guard in terms of anticipating and avoiding potential complications related to anomalies of the posterior capsule.⁸⁹ These patients may have posterior lentiglobusa progressive,⁹⁰ well-demarcated protrusion of the posterior portion of the lens with associated abnormal thinning of the lens capsule or even pre-existing posterior capsular defects. Sudden lens opacification can result from capsular compromise. The globular shape of the lens can simulate an egg (Fig. 7).⁹¹ Intraoperatively, surgeons may see a “fishtail sign” from movement of lens cortex prolapsing through the posterior capsular defect and in the vitreous cavity or intra-operative posterior capsular flutter.⁹² Posterior lentiglobus is usually a unilateral lens opacity, but can be bilateral, as familial cases have been reported. Of note, this type of cataract has also been referred to as “posterior lenticonus,” but the term lentiglobus is considered anatomically more accurate because the protrusion or bulging is globular and not conical.⁹³ A review of 81 eyes in Chinese patients found that decreased lens thickness and a characteristic posterior capsular plaque morphology, consisting of a well-demarcated margin, gray granules and vacuoles, and heterogeneous nuclear opacity that is denser posteriorly, can be important indicators of a preexisting posterior capsule defect.⁹⁴ Ultrasound biomicroscopy in cases of total infantile cataract can be useful in the preoperative detection of pre-existing posterior capsular defects.⁹⁵ Early identification of posterior lentiglobus is important because it can complicate cataract surgery,⁹⁶ and intraoperative posterior capsular rupture is possible.⁸⁹

Fig. 7 –

Posterior lentiglobus.

4.6. Total

Total cataract refers to the case in which all lens fibers are opacified. A white lens may be noted at presentation or as a result of progression of other types of cataracts. Once B-scan ultrasonography is performed to ensure a normal posterior segment, expeditious surgical management is indicated in most of these cases.

4.7. Other

Other types of primary infantile cataracts include anterior pyramidal,⁹⁷ sutural lens opacities, and pulverulent or punctate lens opacities. Certain cataract morphologies are indicators of certain conditions—such as the bilateral anterior lenticonus type cataracts seen in Alport syndrome^98–100, or the wreath-like congenital cataract reported in association with tetralogy of Fallot.¹⁰¹

4.8. Ocular anomalies associated with infantile cataracts

Awareness of preoperative biometric characteristics can be important in terms of intraocular lens power considerations and monitoring for glaucoma.¹⁰² Differences in the overall morphology of cataractous infant eyes have also been detailed in the literature. Baseline ocular examination of 114 infant eyes with unilateral cataract enrolled in the Infant Aphakia Treatment Study revealed anomalies of other anterior segment structures in less than 10% of patients. Mean corneal diameters, pupil size, and axial lengths were slightly smaller for the affected eyes while corneal steepness was greater than for the fellow eyes.¹⁰³ In a Hungarian study, preoperative biometry data of eyes with unilateral congenital cataract was recorded for a retrospective series of 42 infants with unilateral congenital cataract.¹⁰² Cataractous infant eyes had greater CCT (590 vs. 553 microns), higher average K (46.45 vs. 45.09), and smaller corneal diameter (11.0 vs. 11.5) than fellow eyes, but there was not a significant difference in axial length.¹⁰² A mailed questionnaire study in Japan found that associated ocular diseases such as strabismus, persistent fetal vasculature, and posterior lenticonus were seen more commonly in cases of unilateral cataract than bilateral cataract, the latter more commonly associated with nystagmus.¹⁰⁴

As part of a prospective study conducted through the Childhood Cataract Program of the Chinese Ministry of Health, Lin et al in 2016 proposed a new classification system for congenital cataracts based on lens opacity locations and anterior segment characteristics.¹⁰⁵ The location of the lens opacity in 428 Chinese patients with congenital cataracts was determined by slit lamp examination and Pentacam analysis. The cataracts were subdivided into 4 different groups: total, anterior, interior, and posterior cataracts. Mean keratometry, corneal astigmatism, central corneal thickness, and anterior chamber depth was measured and compared between groups. The authors found distinct anterior segment characteristics associated with the location of a congenital cataract. Pupillary membranes were noted in half of the patients with anterior cataracts. Patients with total, anterior, or interior cataracts had higher keratometry values than those with either posterior cataracts or clear lens (fellow eye of unilateral congenital cataract patients). Congenital cataract patients had more corneal astigmatism and thicker central corneal thickness values compared with eyes with a clear lens. Patients with anterior cataracts had the most corneal astigmatism, and the amount of astigmatism declined accordingly with more posterior lens opacities. Posterior lentiglobus-type cataracts were nearly always unilateral.¹⁰⁵

5. Etiology

Infantile cataracts can be hereditary or associated with an ocular or systemic syndrome, secondary to metabolic disease or intrauterine infections, or idiopathic. Most unilateral infantile cataracts and about 25%–30% of bilateral infantile cataracts are idiopathic. ^67–71 Tartarella and coworkers in 2014 reviewed the cases of 207 Brazilian children with cataracts, of whom 117 (56.5%) were congenital. Of these, 51.3% were unilateral, and 48.7% were bilateral. The study enumerated etiologies by laterality for the congenital and developmental groups together but not for the congenital group separately. Fourteen of the cases of uni- or bilateral cataracts were hereditary, while 8 were associated with a syndrome (6 with Trisomy 21). There were 17 cases of cataract associated with persistent fetal vasculature, nearly all of these unilateral. There were 18 total cases of cataract associated with an infectious etiology–either congenital rubella or toxoplasmosis. Nearly 3 quarters of all cases (72.5%) were considered idiopathic.⁸⁵

5.1. Hereditary or associated with ocular or systemic syndrome

Inherited cataracts are generally bilateral, but may be asymmetric. It is important to note that not all inherited cataracts are present at the time of birth. Overall, it has been estimated that about 70–75% of bilateral congenital cataracts have a genetic cause;¹⁰⁶ however, it is likely the percentage of idiopathic bilateral congenital cataracts will be even lower as advances are made in identifying additional mutations.¹⁰⁷ Most infantile cataracts are inherited in an autosomal dominant fashion with high penetrance,^71,107,108 but they can also result from autosomal recessive or X-linked inheritance (Norrie disease, Nance-Horan syndrome, Lowe syndrome).⁷⁸ Infantile cataracts can also be associated with other genetic abnormalities such as chromosomal trisomies (13, 18, 21) or deletions (5p, 18p, 18q).⁷¹ Alternatively, infantile cataracts can be part of a syndromic condition primarily affecting a different organ system, for example, renal (Lowe, Alport, Hallerman-Streiff), skeletal (Stickler and Smith-Lemli-Opitz), central nervous system (Marinesco-Sjogren, Zellweger), musculoskeletal (myotonic dystrophy), or dermatologic (Cockayne, incontinentia pigmenti, ichthyosis).^71,109–113 While having a unilateral infantile cataract does not exclude the possibility of systemic syndrome, it makes it much less likely.¹¹⁴

5.2. Metabolic

Metabolic syndromes that may be associated with cataract presence or formation in this age range include diabetes mellitus, galactosemia, galactokinase deficiency, and hypoglycemia.^71,115 Other less common metabolic causes of pediatric cataracts include: peroxisome biogenesis disorder 14B, lathosterolosis, cerebrotendinous xanthomatosis, and stomatin-deficient cryohydrocytosis/ GLUT1 deficiency syndrome with pseudohyperkalemia and hemolysis. Some of these disorders can be treated with dietary changes or medications. Genetic screening can help to identify these disorders before patients develop systemic abnormalities.

5.3. Infectious

TORCH pathogens (Toxoplasma, Rubella, Cytomegalovirus, Herpes simplex, and Other) may result in cataract formation.^71,116–118 Herpes simplex virus and Rubella are the most common infectious causes of congenital cataract.¹⁰⁶ Infections with TORCH pathogens such as HSV may affect the ectodermal tissues from which the lens is derived.¹¹⁹ Lu and Yang in 2016 compared serum test results for IgM and IgG antibodies to TORCH pathogens in 69 Chinese children with congenital cataract and for 5,914 children in a control group and found that HSV II IgG positivity rates significantly differed between the cataract and control groups.¹¹⁹ While Rubella infections are now uncommon in the United States and Europe due to widespread vaccination, congenital rubella syndrome is still an important consideration in the developing world¹²⁰ and for infants with cataracts, heart defects, deafness, and/or other anomalies whose mothers have not been vaccinated and were infected during the first trimester of pregnancy. A 2014 study assessing the intraoperative and long-term outcomes of cataract surgery in children with congenital rubella syndrome in India showed that good visual outcomes could be achieved.¹²⁰

5.4. Idiopathic

If an apparent cause for an infantile cataract cannot be determined, the lens opacity may be described as idiopathic. Secondary cataracts associated with uveitis, intraocular tumors, chronic retinal detachment, or from iatrogenic causes such as radiation, systemic steroids, vitrectomy, or laser for retinopathy of prematurity are possible but uncommon in the under 18 months age group. Trauma, while less likely as an etiology of cataract in an infant, is always possible, as many injuries in young children may be unwitnessed.

6. Work-up

6.1. Clinical history and ocular examination

In addition to obtaining a careful prenatal and developmental history, reviewing serial personal photographs of the infant may be helpful in determining whether cataracts are congenital or acquired.^121,122 Ascertaining any family history of cataracts in infancy or childhood or other ocular pathology is essential, as familial cataracts tend to be bilateral and dominantly inherited. Knowing if there is a parental ocular history of anterior segment dysgenesis, aniridia, glaucoma, or inherited retinal disease can be helpful in anticipating a patient’s clinical course. Careful slit lamp examination of an affected infant’s parents’ eyes can determine if similar pathology exists and may aid in determining mode of inheritance. Certain types of cataracts such as punctate lens opacities may be missed unless the parents’ eyes are dilated.¹²²

Careful anterior segment examination of the patient’s eyes, often requiring the use of handheld instruments, can allow detection of key morphological differences and the presence of associated ocular anomalies such as aniridia, anterior segment dysgenesis, coloboma, or persistent fetal vasculature.¹²³ Ultrasound biomicroscopy can be helpful in determining if a patient is aniridic or if a preexisting posterior capsular defect is present. Funduscopic examination in the setting of a partial or less dense cataract is important in detecting posterior segment pathology that may limit visual outcome.¹²² B-scan ultrasonography must be performed when the posterior segment cannot be directly visualized. Longitudinal views are important in evaluating for the characteristic thin, reflective membrane or stalk-like appearance of persistent fetal vasculature spanning from optic nerve head to the posterior lens.

6.2. Laboratory

While TORCH testing for infectious causes may be revealing in a few cases, it has a low yield.¹²⁴ It may be more appropriate to consider targeted testing of components of the TORCH screen on a case-by-case basis following a detailed maternal antenatal history and taking into consideration a child’s comorbidities and vaccination status. In cases of early onset glaucoma or a family history of Lowe syndrome, a urine sample should be obtained for amino acid testing. Bloodwork is most easily drawn at the time of surgery in cases of bilateral, nonhereditary infantile cataracts to investigate for systemic or metabolic causes.

6.3. Molecular genetic

History, clinical examination, and family preferences should inform decisions about genetic testing. For example, an infant with congenital cataracts in the setting of family history of vascular dissection may lead to an investigation for collagen gene defects. Molecular genetic analysis is now allowing the many variations of infantile cataracts to be identified, categorized, and associated with genetic etiologies and/or systemic syndromes in ways not previously possible (Fig. 8). More than 100 genetic mutations leading to hereditary cataract have been identified so far.¹⁰⁶ Many of these mutations are associated with problems with the lens microarchitecture.¹²⁵ About half of childhood cataracts are caused by mutations in genes that code for proteins involved in lens structure or clarity.⁷⁸ The hereditary congenital cataract genes have been grouped into 2 major categories: 1) mutations in genes encoding enzymes (e.g. galactosemia, lathosterolosis, ABHD5-related ichthyosis, etc.) and 2) mutations in genes encoding structural proteins. These include mutations in the genes coding for alpha- and beta/gamma-crystallins, genes encoding membrane associated proteins such as connexins, aquaporin/ MIP (major intrinsic protein of lens fibers), and other membrane-associated proteins, genes encoding cytoskeletal proteins, and genes encoding DNA- or RNA-binding proteins.¹²⁵

Fig. 8 –

Congenital cataracts in the right (A) and left and (B) eyes of a 4- week old boy. There was no family history of congenital cataracts. His cataracts were membranous at the time of cataract surgery and Lowe syndrome was suspected. However, genetic testing revealed a pathogenic mutation (c.97C>T) in the first exon of the major intrinsic protein of the ocular lens fiber membrane (MIP) gene which has been shown to be associated with autosomal dominant congenital cataracts and a normal OCRL gene. The bottom left and right photos show similar looking congenital cataracts in the right eye (C) and left eye (D) of an infant with Lowe syndrome.

Cataract-targeted next-generation sequencing (NGS) has been shown to be an efficient means of diagnosis for inherited congenital cataract⁷² and has expanded the mutational spectrum in genes known to cause congenital cataracts.¹²⁶ Gillespie and coworkers evaluated 36 individuals with nonsyndromic or syndromic bilateral congenital cataracts and found a genetic cause in 3 quarters of the patients. Eighty-five percent of patients who had nonsyndromic congenital cataracts were determined to have likely pathogenic mutations occurring in highly conserved domains that are essential for normal protein functioning.⁷² Over 60% of patients with syndromic congenital cataracts also had potentially pathogenic mutations. Given the ways in which NGS affected and informed clinical management of the study patients, the authors contend that NGS should be performed routinely for patients with bilateral congenital cataracts. Advancing genotype-phenotype correlations will also provide greater insight into cataractogenic mechanisms.⁷² Next-generation sequencing has also been used to expedite the diagnosis of cataracts in children associated with inborn errors of metabolism such as galactosemia, cerebrotendinous xanthomatosis, and disorders of cholesterol or peroxisome biogenesis.¹²⁷ Congenital cataract panel testing for up to 38 genes is now available commercially in the United States (Table 1), and in the United Kingdom there are 3 centers for molecular genetic testing for ocular disorders. A 142 gene cataract and lens abnormalities panel is available through ManGen Opthalmic Disorders (mangen.co.uk).

Table 1 –

Genes tested with commercially available congenital cataract and cataract panels in USA.

Crystallins	CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBB1, CRYBB2, CRYBB3, CRYBA4, CRYGB, CRYGC, CRYGD, CRYGS
Connexins	GJA1, GJA3, GJA8
Transcription Factors	FOXC1, FOXE3, HMX1,HSF4, MAF, PAX6, PITX 2, PITX3, SIX6, TFAP2A, VSX2
Membrane Proteins	BEST1, LIM2, MIP, SLC16A12, SLC33A1,TMEM70
Cytoskeletal structural proteins	BFSP1, BFSP2, NHS, VIM
Collagen	COL11A1, COL2A1, COL4A1, COL4A2
Other	ABCA3, ADAMTSL4, AGK, AKR1E2, ALDH18A1, BCOR,CHMP4B, CTDP1, CYP27A1, CYP51A1, EOGT, EPG5, EPHA2, EYA1, FAM126A, FTL, FYCO1, FZD4, GALK1, GCNT2, GFER, JAM3, LONP1, LSS, MIR184, MYH9, NDP, NF2, OCRL, OPA3, P3H2, PXDN, RAB18, RAB3GAP1, RAB3GAP2, RECQL4, RGS6, RNLS, RRAGA, SC5D, SIL1, SIPA1L3, TBC1D20, TDRD7, UNC45B, WDR87, WFS1,WRN
Representative Metabolic	Aniridia (PAX6)
Disorders or Syndromes	Ayme-Gripp syndrome (MAF) Axenfeld-Rieger syndrome (PITX2) Cataract-microcornea syndrome (ABCA3) Galactokinase deficiency with cataracts (GALK1) Hypomyelination with congenital cataract (FAM126A) Lowe syndrome (OCRL) Marinesco-Sjogren syndrome (SIL1) Sengers syndrome (AGK) Severe myopia with cataract and vitreoretinal degeneration (P3H2)

Websites:

www.invitae.com

www.genedx.com

www.preventiongenetics.com

7. Management

The clinical decision to operate or not to operate for an infantile cataract depends on the anticipated visual significance of the lens opacity. The decision to operate and the timing of surgery also depend on whether a cataract is unilateral or bilateral, the morphology of the lens opacity, and its size, position, and density.⁷¹ A visually significant cataract may be defined as a 3 mm or larger central opacity.¹⁰³ Optimal management of infantile cataracts involves long-term care¹²⁸ and families should be counseled accordingly, made aware of the treatment options, and enlisted in the decision making process. Surgery for infantile cataract has been described as an initial step in the journey of optically rehabilitating an affected eye.¹²⁹

7.1. Nonsurgical

While most infantile cataracts will require surgery to clear the visual axis and stimulate development of the visual system, some cataracts may be amenable to observation. Examples would include small, anterior polar cataracts, as they are of minimal visual significance, or cataracts associated with severe forms of microphthalmia, microcornea, or PFV, as they may have a higher risk of post-lensectomy glaucoma or other postoperative complications, and cataract extraction might not result in a better visual outcome.¹³⁰

8. Surgical

8.1. Timing of surgery

Despite the potentially significant risks of cataract surgery in the youngest infants, delaying or foregoing surgery leads to irreversible deprivation amblyopia.¹³¹ The optimal timing of infantile cataract surgery has been investigated and debated for many years. In 1996, Birch and Stager demonstrated that visual prognosis for a child with a unilateral cataract may be improved by surgery before 6 weeks of age.¹³² Prior to 6 weeks of age, referred to as the latent period, vision loss due to form deprivation does not occur because the immature visual system is still reliant on subcortical pathways.^71,133 A subsequent study showed that the latent period for bilateral visual deprivation may be as long as 10 weeks.¹³⁴ The absence of preoperative nystagmus was shown to be a better indicator of visual outcome than age.¹³⁴ In 2009, Birch et al examined the critical period for surgical treatment of dense, congenital bilateral infantile cataracts and did not find a latent period. During weeks 0–14, mean visual acuity decreased by 1 line with each 3-weeks delay in surgery.¹³⁵ While surgery after 4 weeks of age was associated with greater prevalence of strabismus and nystagmus than surgery before 4 weeks, surgery during the first 4 weeks of life was associated with more secondary membrane formation and glaucoma.¹³⁵ This was confirmed by more recent studies as well. One study of 147 eyes with congenital cataract in Victoria, Australia, found that the incidence rate of glaucoma was highest for surgery performed within first month of life, and the risk of glaucoma decreased with increasing months of age at operation.¹³⁶ Therefore, it is likely prudent to defer surgery until at least one month of age.¹⁰³

In summary, the timing of surgery for infantile cataract involves balancing the risks of early surgery (intraoperative risks, development of glaucoma) versus those of waiting (amblyopia) (Table 2). For settings in which patients are presenting at relatively older ages, one Chinese study hypothesized there might be some benefit in delaying surgery in cases of bilateral, total infantile cataracts up until 6 months of age as the authors found no advantage to doing surgery at 3 months compared with 6 months;¹³⁷ however, other clinicians have not corroborated these findings.

Table 2 –

Pros and cons of infantile cataract surgery at different ages.²⁶⁸

	Pros	Cons
<4 wk	Good visual potential*	High risk of glaucoma/glaucoma suspect
	Reduced risk of strabismus	Increased risk of postoperative apnea
	Potential for stereopsis
4–8 wk	Good visual potential178, 195, 269, 270
	Reduced risk of strabismus255
	Potential for stereopsis271
	Moderate risk of glaucoma/glaucoma suspect190,191
>8 wk	Low risk of glaucoma/glaucoma suspect190,191	Reduced Visual Potential178, 195,270
		High risk of strabismus 255
		Reduced potential for stereopsis254

^*The differences between unilateral and bilateral cataract surgeries are not well established.

8.2. Immediate versus delayed sequential

The relative advantages and disadvantages of immediate versus delayed sequential surgery have been debated. Potential advantages to immediate sequential surgery, particularly when performing cataract surgery for the youngest infants, include better visual outcome due to earlier visual rehabilitation of the “second” eye, conceivably lower anesthetic risk, and arguably lower cost. A retrospective study of 40 patients who had undergone bilateral congenital cataract extraction in a single surgery session in Naples, Italy, revealed no significant adverse effects leading to the suggestion that simultaneous surgery in bilateral congenital cataract might not need to be limited to patients with significant anesthetic risk.¹³⁸ Dave et al also found that simultaneous bilateral cataract resulted in no discernible difference in the incidence of adverse events or visual outcomes but noted that their findings were limited by their small sample size.¹³⁹ A study of 344 bilateral, simultaneous vitreoretinal surgery surgeries performed in pediatric patients found this type of surgery to be a “feasible and safe” treatment paradigm for patients with a high anesthesia risk profile.¹⁴⁰ Most recently, a retrospective Austrian study of 220 patients with mean age at surgery of 15.94 months found no significant difference in intraoperative or postoperative complications in patients undergoing simultaneous bilateral cataract surgery, compared with children undergoing unilateral or staged cataract procedures.¹⁴¹

While acknowledging the potential advantages of immediate sequential surgery, critics have noted that complications associated with immediate sequential surgery could lead to bilateral blindness. One difficulty of studying the likelihood of such an outcome is that endophthalmitis after congenital cataract surgery is so rare that the sample size for any study attempting to establish safety would have to be enormous to show a difference.¹⁴² Therefore, in situations in which immediate sequential surgery is performed, surgeons should proceed with utmost caution, treating each eye as a separate surgical case, with separate set-ups (drapes, instrument rays, bottles of balanced salt soltion and viscoelastic agents from different batches) for each eye.¹⁴³

9. Techniques

9.1. Anesthesia risk

Surgery for infantile cataracts is performed under general anesthesia. The incidence of oculocardiac reflex was 50% during congenital cataract surgery in one series.¹⁴⁴ Concerns about the neurotoxicity of general anesthesia, particularly in the setting of very early surgery, have prompted review of the animal and human data. While animal studies of general anesthesia in young rodents and nonhuman primates did show neurotoxic effects, prospective clinical trials in humans do not demonstrate lower intelligence quotients in children less than 3 years who had isolated or short exposures to general anesthesia.¹⁴⁵ Current research efforts to minimize potential adverse effects of general anesthesia are underway, including the possible addition of protective agents to the anesthetic mix.¹⁴⁵ Postoperative examinations under anesthesia may occasionally be necessary to diagnose and treat any complications but these should be minimized to the extent possible given the potential risks of anesthesia in early infancy.

9.2. Surgical approach

9.2.1. Lensectomy and anterior vitrectomy

Many surgeries for infantile cataracts involve the use of a vitreous cutting instrument and an anterior chamber maintainer (see discussion below).^{146,147,148,149} A 2-port technique makes it possible to perform either an anterior vitrectorrhexis or manual capsulorrhexis followed by lens extraction with posterior capsulotomy and anterior vitrectomy. If no intraocular lens (IOL) is to be placed, 2 superior stab incisions are created at the superior or temporal limbus. An infusion cannula is placed through one and the vitreous cutter through other. An anterior capsulectomy at least 5 mm in diameter is created with the vitrector. While manual capsulorrhexis is possible in the 12 months and under age group, it is technically challenging. Tension on the created flap must be directed centrally to avoid rapid radial extension of the capsule. Alternative approaches to producing an appropriately sized capsulorrhexis opening include a 2-incision push-pull manual capsulotomy technique¹⁵⁰ and bipolar diathermy capsulotomy. Regardless of method chosen, hyperinflation of the anterior chamber with viscoelastic is essential in the youngest children to control the rhexis tear.¹⁵⁰ The propensity for radial extension during rhexis formation is high due to the elasticity of the pediatric lens capsule.¹⁵⁰ After aspiration of the lens material, a posterior capsular opening at least 4 mm in diameter is created using one of the rhexis techniques described above. The posterior capsular opening can be created through either a limbal or a pars plicata approach. A limited anterior vitrectomy is then performed, followed by wound closure with 9–0 or 10–0 absorbable sutures. A peripheral iridotomy can be performed with the vitrector in selected cases to prevent pupillary block glaucoma. Subconjunctival or intracameral antibiotics (see discussion below under Medication management) and corticosteroids are then administered as well as one drop of a cycloplegic ophthalmic solution, an antibiotic/steroid ointment, and an eye patch and shield.

9.2.2. Lensectomy and anterior vitrectomy with placement of intraocular lens

If an intraocular lens is to be placed, either 2 clear corneal stab incisions are made or a scleral tunnel and a stab incision for the irrigation cannula is created. An anterior capsulotomy at least 5 mm in size is then created with either the vitrector or manually with forceps. Aspiration of the lens is performed with the vitreous cutting instrument. One corneal stab incision or the scleral tunnel is then enlarged with a keratome, viscoelastic is instilled in the anterior chamber, and the intraocular lens is inserted into the capsular bag. The wounds are closed using 9–0 or 10–0 absorbable sutures and the ophthalmic viscoelastic device is removed. At the end of the case, one drop of cycloplegic ophthalmic solution, an antibiotic/steroid ointment, an eye patch and shield are applied to the operated eye.¹⁰³

The choice of surgical technique for IOL placement hinges on the presence and quality of available capsular and zonular support.¹⁵¹ While capsular bag implantation is always preferred, sulcus fixation of a foldable 3-piece lens may also be possible. A posterior optic capture technique can be considered when a 3-piece intraocular lens is implanted in the setting of good capsular support.^152–157 This technique can help ensure centration and stabilization of the lens and counteract capsular phimosis and visual axis opacification.^151–155 Anterior chamber intraocular lenses and pre- and retropupillary iris-claw IOL technique are not routinely recommended or used in children—particularly in the setting of surgery for infantile cataract–due to issues with long-term fixation stability, dislocation, and significant associated complications.¹⁵¹ Similarly, in the setting of limited or no capsular support, sutured intraocular lenses have a finite lifespan with high rates of lens decentration, suture degradation, and vitreoretinal complications and currently are rarely placed.¹⁵¹

9.2.3. Use of smaller instrumentation

In the past, 20-G vitrectors were often used to perform lensectomies in infants; however the large instrumentation size and small anterior chamber and low scleral rigidity of small infants often resulted in corneal haze at wound sites, inadvertent capsular compromise, wound leakage with or without iris prolapse, and vitreous incarceration in the wound.¹⁵⁸ Most pediatric surgeons now use 23G¹⁴⁶ and 25 G vitrectors.^147,148,149 In 2009, Chee and Lam described management of congenital cataract in children younger than 1 year using a 25-gauge vitrectomy system.¹⁴⁷ Li et al described minimally invasive 23G vitrectomy via a corneal approach for the treatment of pediatric cataract.¹⁴⁶ Tartarella and Fortes Filho reported on the outcomes of transconjunctival pars plicata 25-G instrumentation to perform minimally invasive, sutureless lensectomy in infants with congenital cataract.¹⁴⁸ Raina et al 2016 compared transcorneal and pars plana routes in pediatric cataract surgery in infants using a 25-G vitrectomy system.¹⁴⁹

9.3. Posterior capsule management

Posterior capsulectomy and anterior vitrectomy can be performed through either a limbal approach prior to IOL insertion or a pars plicata approach after the IOL is implanted in the capsular bag. Various approaches to posterior capsular management have been described, as this is a critical component influencing the outcome of surgery for infantile cataract. Adequate capsulotomy size is a balance of the need for stable intraocular lens fixation balanced against the risk of subsequent visual axis opacification. Children under 3 years old should always have a primary posterior capsulectomy and anterior vitrectomy performed, while for children 3–7 years of age a primary posterior capsulectomy without vitrectomy can be considered.¹⁵⁹

Vasavada and coworkers performed a systematic review in 2011 of newer options for minimizing posterior capsular opacification/ visual axis opacification after cataract surgery in these very young patients.¹⁵⁹ These include pars plicata posterior capsulorhexis, sutureless 23- or 25-G vitrectomy, sealed-capsule irrigation to selectively and specifically target lens epithelial cells,^160,161 and bag-in-the-lens IOL. In the “bag-in-the-lens” technique, the anterior and posterior continuous curvilinear capsulorhexis are made the same size so that the IOL is supported by both lips that tightly encircle the IOL optic in a circumferential interhaptic groove.¹⁶² This IOL design creates a seal between the anterior and posterior capsular rims that prevents lens epithelial cells from migrating to the anterior vitreous. This approach was shown to help minimize the need for an anterior vitrectomy, even in children younger than 2 years of age.¹⁶²

The presence of a preexisting posterior capsular defect in the context of posterior capsular plaque necessitates extra care. Hydrodissection should be avoided in these cases as the sudden increase in pressure can cause uncontrolled tearing of a pre-existing posterior capsular defect and send lens material into the posterior segment.⁹³ While it is sometimes possible to convert a pre-existing posterior capsular defect into effective posterior capsular support (Fig. 9), it is important to avoid enlarging the opening too much. Careful incision making and the use of a low infusion rate may promote chamber stability and reduce the chance of uncontrolled peripheral extension of the preexisting posterior capsular defect.¹⁵⁹ For posterior capsular plaque, plaque peeling, or vitrectorhexis can be performed, depending on the extent of the plaque.¹⁵⁹

Fig. 9 –

(A) Large, pre-existing posterior capsular defect in patient with posterior polar type cataract. (B) Care taken to avoid excessive enlargement of defect during lens removal can permit placement of an intraocular lens in the capsular bag.

In the setting of persistent fetal vasculature, intraocular scissors may be required to excise a dense posterior plaque and endocautery can be utilized to prevent hemorrhage when cutting the fibrovascular stalk. Because of possible extension of the retina anterior to the pars plicata, a limbal approach may be advisable in cases in which a fibrovascular membrane obscures the surgeon’s view.⁸⁷ The use of standard pars plicata sclerotomies or total excision of the retrolental fibrovascular membrane could result in inadvertent retinal excision in these cases;¹⁶³ however, contraction of residual fibrovascular membrane left in place may result in pupillary distortion and/or occlusion, potentially exerting traction on the peripheral retina and leading to retinal detachment. More severe cases of PFV, for example, those with a very small eye, elongated ciliary processes, or evidence of tractional retinal detachment, are best managed in conjunction with a pediatric retina specialist given the high likelihood of posterior segment complications.

9.4. Medication management

A standard postoperative eye drop regimen includes topical prednisolone acetate 1% at least 4 times a day for a minimum of 1 month, but not longer than 6 months, after surgery, topical antibiotic 3–4 /day for one week, and a cycloplegic eye drop (twice a day for 2–4 weeks after surgery.¹⁰³ The use of intracameral moxifloxacin (250 micrograms) for endophthalmitis prophylaxis in pediatric patients has been investigated and may have equivalent safety outcomes when compared with subconjunctival antibiotics.¹⁶⁴

The use of alternative or additional steroid medications in conjunction with infantile cataract surgery has also been explored.^{165,166–168} Steroid injection to the orbital floor to help reduce the inflammatory response is an option at the end of the infant cataract surgery. The use of intracameral triamcinolone acetonide during pediatric cataract surgery can be helpful in visualizing the vitreous and has the added benefit of decreasing postoperative inflammation.^167,169,170 A study of 53 eyes of children < 2 years old undergoing congenital cataract surgery in Brazil found that injection of 1.2 mg of intracmeral triamcinolone at the end of the case did not significantly affect intraocular pressure or central corneal thickness in the first postoperative year.¹⁷¹ The use of intracameral dexamethasone was not found to be associated with an increased risk of glaucoma in another study (median follow up 38 months).¹⁷² Ventura and coworkers compared the use of intraoperative intracameral triamcinolone versus postoperative oral prednisolone to address intraocular inflammation in patients with a mean age of 10 months having congenital cataract surgery¹⁶⁵ and found similar outcomes; however, the rationale for using oral prednisolone has been questioned,¹⁶⁶ given the effectiveness of subconjunctival and topical steroid drops and the potential side effects of systemic steroids.

While adrenal suppression in infants treated with topical ocular glucocorticoids has been reported,^168,173 the doses used in the reports were not comparable to those routinely used in the United States after routine infantile cataract surgery.¹⁷⁴ Nevertheless, pediatric cataract surgeons should be aware of the potentially serious systemic side effects of topical steroid use in infancy and closely monitor children using topical corticosteroids.¹⁷³

10. Postoperative complications

Cataract surgery can be successfully managed in even the youngest patients with personalized care and experienced teamwork.^{122, 175} Age at time of surgery and type of cataract may have predictive value in terms of the likelihood of complications for a given patient.¹³¹ Concomitant eye pathology also plays a role although it is important to note that even microphthalmic eyes can do well after early surgical intervention.¹⁷⁶ Complication rates vary according to whether patients are left aphakic or receive primary IOL implantation.⁷⁷ The increased inflammatory response in infant patients is commonly associated with lens reproliferation into the visual axis and pupillary membrane formation/visual axis opacification.^175,177,178 This may result in corectopia. Vitreous prolapse and pupillary membrane formation can lead to early pupillary block glaucoma. Patients having cataract surgery in infancy are at relatively higher risk of developing glaucoma.¹⁷⁸ Posterior synechiae may be more common in pseudophakic eyes.¹⁷⁹ Less common events are intraoperative bleeding and retinal detachment, endophthalmitis, and toxic anterior segment syndrome.¹³¹ Contact lens-associated complications such as corneal ulceration or transient corneal edema are also possible.¹⁷⁵

10.1. Lens reproliferation into the visual axis and pupillary membrane formation

Lens reproliferation with visual axis opacification (VAO) is the most common complication of infantile cataract surgery. At 1 year and 5 years into the IATS, the most common postoperative complication of surgery for unilateral, infantile cataract was lens reproliferation into the visual axis and pupillary membrane.^{77, 180} The most common additional intraocular surgery required was clearing the VAO, and this procedure was more frequently required in the patients receiving primary intraocular lens implantation.⁷⁷ The 5-year results of the IoLunder2 study showed a 5 times higher risk of reoperation for visual axis opacity in children with bilateral cataract and a 20X higher risk in children with unilateral cataract.¹⁸¹ Negalur and coworkers reported that 13/69 eyes (18.8%) having primary IOL implantation under 6 months of age developed VAO and required membranectomy at a median of 6 months following initial surgery.¹⁸² Interestingly, the development of VAO was not associated with age at surgery.¹⁸² Vasavada and coworkers reported a lower incidence of visual axis opacities requiring surgery (8% in the aphakic group and 10.3% in the pseudophakic group) in their randomized controlled clinical trial describing 5 year outcomes of bilateral aphakia and pseudophakia in 60 children up to 2 years of age.¹⁷⁹ This may have been partly due to an older median age of children undergoing IOL implantation than in the IATS (Vasavada study = 6 mos; IATS = 1.8 months).¹⁸³

Because of the high likelihood of lens reproliferation and pupillary membrane formation, primary posterior capsulotomy is recommended for any child for whom in-office NdYAG capsulotomy is not likely to be possible. While in some situations subsequent NdYAG capsulotomy in the operating room might be feasible, doing so requires the patient to undergo another general anesthesia and involves repositioning an intubated, supine child into an upright position or turning the head laterally for YAG capsulotomy.^184,185 Performing vitrectomy can also lower posterior capsular opacification and reoperation risk, according to a 2019 meta-analysis of 11 randomized controlled clinical trials including 634 eyes with congenital cataract.¹⁸⁶ In addition, attempting to reduce the amount of visual axis opacification is an area of active research. Current molecular studies are investigating the preoperative profile of inflammatory factors and their correlations with postoperative inflammatory responses in patients with congenital cataract.¹⁸⁷ Such work could enable prediction of individual postoperative inflammatory response and improve postoperative antiinflammatory management. Furthermore, femtolaser assisted capsulectomy may facilitate more accurate sizing of the rhexis needed for the “bag-in-the-lens” technique, a technique that may help prevent posterior capsule opacification, in children.¹⁶²

10.2. Glaucoma

Glaucoma remains a major sight-threatening complication after cataract surgery in infancy,^188–191 particularly in resource-poor settings.³⁰ One 28-year longitudinal case series reported an overall glaucoma rate of one-third, with secondary glaucoma developing between 3 months and 16.5 years postsurgery.¹⁹² At 5 years postoperatively in the Vasavada and coworkers study, the incidence of glaucoma was 16% and 13.8% in the bilaterally aphakic and pseudophakic groups, respectively.¹⁷⁹ Negalur and coworkers reported that 2/69 (2.9%) of eyes of patients under 6 months of age having primary IOL implantation had glaucoma, and 2/69 had ocular hypertension, with a minimum 3 year follow-up period after surgery.¹⁸² Glaucoma plus glaucoma suspect was diagnosed in 40% of eyes in both the intraocular lens and contact lens groups at 10 years in the Infant Aphakia Treatment Study (IATS).¹⁹³ The IoLunder2 Study, reporting data for 235 children having cataract surgery under 2 years of age, found that 20% of children with bilateral cataract and 12% of children with unilateral cataract had developed secondary glaucoma within 5 years after cataract surgery.¹⁹⁴ Furthermore, intraocular lens implantation was not found to be protective against glaucoma.¹⁸¹

The Glaucoma Research Network/World Glaucoma Association defined childhood glaucoma as “intraocular pressure (IOP) greater than 21 mm Hg with one or more of the following anatomic changes: 1) corneal enlargement; 2) asymmetrical progressive myopic shift coupled with enlargement of the corneal diameter and/or axial length; 3) increased optic nerve cupping defined as an increase of 0.2 or more in the cup-to-disc ratio; or 4) the use of a surgical procedure for IOP control. Glaucoma suspect is defined as 1) 2 consecutive IOP measurements about 21 mm Hg on different dates after topical corticosteroids had been discontinued without any of the anatomical changes listed previously; or 2) took glaucoma medications to control IOP without experiencing any of the anatomical changes listed previously.^195,196 With regards to the discussion that follows, it is important to note that not all studies have utilized this standardized definition of childhood glaucoma, to some extent limiting the generalizations we are able to make from the available data.

Numerous studies have investigated putative predictive factors for glaucoma in patients having surgery for congenital and infantile cataract.^{136,190,192–194,197–201} The resulting data has shown that the complication of glaucoma is not uncommon and that the youngest children having surgery for infantile cataract have the highest risk of developing glaucoma.¹⁹⁰ Multiple studies have found a higher risk of glaucoma in patients having early cataract surgery.^{136,190,194,197–199} Haargaard and coworkers reported a 7.2-fold increased risk for glaucoma after cataract surgery performed for patients less than 9 months of age.¹⁹⁷ Balekudaru and coworkers in a prospective, longitudinal cohort study of 101 eyes, found age < 3 months at time of surgery for patients left aphakic to be the only identifiable risk factor for glaucoma.¹⁹⁸ Mataftsi and coworkers conducted a large meta-analysis evaluating timing of infantile cataract surgery and effect of primary IOL implantation on the incidence of postoperative glaucoma. They found that of 470 individual patients having cataract surgery at a median age of 3 months, 17% developed glaucoma at a median follow up of 4.3 years.¹⁹⁹ Primary IOL implantation appeared to lower glaucoma risk while surgery at 4 weeks of age or younger and additional procedures appeared to increase the risk of glaucoma in these patients.¹⁹⁹ Evaluation of glaucoma-related adverse events at 1, 5, and 10.5 years in the IATS, however, did not show primary intraocular lens placement to be a mitigating factor.^190,193

Other factors that have been identified as potential risk factors for the development of glaucoma after surgery for infantile cataract in some studies include bilateral aphakia,^136,192 decreased corneal diameter,¹⁹² and/or decreased axial length of the affected eye.²⁰⁰ Kim and coworkers reported the long-term cumulative risk of postoperative glaucoma in 38 microphthalmic eyes of 19 children with bilateral cataract to be 32% by 10 years after surgery at a mean age of 3.2 ± 1.7 months.²⁰⁰ While an association between cataract morphology (fetal nuclear, persistent fetal vasculature) and glaucoma risk has been suspected, the IATS was unable to find an increased risk of glaucoma or glaucoma in infantile eyes with a diagnosis of PFV or fetal nuclear cataract that underwent unilateral congenital cataract surgery.²⁰¹ This may have been due to the fact that only mild cases of persistent fetal vasculature were included in the IATS. The IoLunder 2 cohort study also did not find an association between cataract type and the development of glaucoma.¹⁹⁴ Finally, the role of surgeon experience has been questioned but not shown.

Children who have undergone surgery for infantile cataract require lifelong surveillance as glaucoma may develop over a decade later.^{188,192,200,202} With regards to management of children who develop glaucoma after surgery for infantile cataract, rebound tonometry (ICare tonometer) is generally well-accepted by unsedated pediatric patients but may overestimate intraocular pressure compared with measurements obtained by applanation tonometry.^203,204 Furthermore, as central corneal thickness increases, the differences in readings obtained between the 2 devices will further diverge.²⁰³ Children with glaucoma after congenital cataract surgery tend to have worse vision and require more medications to control their intraocular pressure compared with children with primary congenital glaucoma.²⁰⁵ Early diagnosis and appropriate management can still lead to good visual outcomes for children with aphakic glaucoma.²⁰⁶ Of note, a significant number of these patients will require surgical intervention for intraocular pressure control.²⁰⁶ When intraocular surgery becomes necessary to control IOP in pediatric aphakic glaucoma, trabeculotomy and/or goniotomy can be effective in most eyes and may lessen the need for filtering and shunting procedures;²⁰⁷ however, some pediatric glaucoma surgeons may prefer aqueous implant surgery for aphakic glaucoma.

10.3. Retinal detachment

Retinal detachment following surgery for infantile cataract is an uncommon occurrence, but can occur, particularly in the setting of severe PFV. Only 3 eyes in the IATS were reported to have this complication—2 eyes in the contact lens arm of the study at year 1 and 1 eye after undergoing a pars plana membranectomy and the second after being treated for endophthalmitis. Both of these eyes had poor vision, and 1 eye developed phthisis bulbi.¹⁹⁵ During years 6–10, 1 eye in the IOL group additionally developed a retinal detachment. Of note, this patient had been diagnosed with Stickler syndrome.¹⁷⁵ There were no cases of retinal detachment in the Negalur and coworkers series of 69 eyes of 38 infants undergoing primary IOL implantation under 6 months of age.¹⁸²

10.4. Endophthalmitis

An international online survey regarding endophthalmitis following pediatric cataract surgery was conducted in 2018.²⁰⁸ Although the inquiry was not specific to infantile cataracts, of 237 ophthalmologists (all members of the American Association for Pediatric Ophthalmology and Strabismus) who responded, 8 (3.4%) reported 22 cases of endophthalmitis following pediatric cataract surgery.²⁰⁸ Photophobia (50%) and pain (41%) were the most common presenting symptoms, and conjunctival injection (36%) and hypopyon (32%) were the most common presenting signs.²⁰⁸ Staphylococcus aureus grew in 32% of cases, and the endophthalmitis was managed with intravitreal, systemic, and topical antibiotics in about a third of cases. About two-thirds of ophthalmologists reported having administered prophylactic intracameral antibiotics during surgery. The authors of the study recommended early postoperative evaluation, subsequent follow-up visits, and a high index of suspicion to facilitate recognition of endophthalmitis in this setting.²⁰⁸

A more recent population-based retrospective cohort study evaluated endophthalmitis within 90 days after pediatric cataract surgery in the United States using the Optum Insurance Claims Database. Fifty-eight million deidentified charts were reviewed of patients under 13 years of age who underwent cataract surgery in one or both eyes with or without primary intraocular lens implantation between 2003 and 2017. Traumatic cataracts were excluded. Of 789 eyes having cataract surgery, 67% of those receiving an IOL, endophthalmitis was diagnosed in 4 eyes (0.51%). Median time to diagnosis was 6.5 days.²⁰⁹

10.5. Toxic anterior segment syndrome

There are few published reports of toxic anterior segment syndrome (TASS) following infantile cataract surgery. In one series of 893 eyes of 534 patients undergoing pediatric cataract surgery in Turkey, TASS was described in 19 eyes of 13 patients, and 5 of these patients were 12 months or younger.²¹⁰ The occurrence of TASS was attributed to ethylene oxide sterilized vitrectomy packs in this series.²¹⁰ The risk of TASS occurring is thought to be lower in pediatric cataract surgery settings which tend not to have the higher turnover rates of adult ambulatory surgery centers; however, the risk should be considered particularly in settings in which bilateral, simultaneous pediatric cataract surgery is performed since both eyes could be at risk of significant vision loss.

10.6. Other adverse events

Other adverse events described after infantile cataract surgery have included IOL deposits and IOL decentration,¹⁸² corectopia, vitreous, or retinal hemorrhage, hyphema, retained cortex, phthisis bulbi, contact-lens associated keratitis, corneal abrasion, corneal opacity associated with tight contact lens, capsular phimosis, wound leak/ dehiscence.¹⁸⁰

10.7. Need for additional surgeries

At the 10 year follow-up in the IATS, the IOL group had undergone more additional intraocular surgeries (n = 71) than the aphakia group (n = 38), although the difference was less than it had been at 5-year follow-up (66 surgeries vs. 17 surgeries).¹⁷⁵ The reasons for the increase in subsequent surgeries during the 6–10 year follow up period were that more cases of glaucoma were diagnosed, many aphakic children were electing to undergo secondary IOL implantation, and a growing number of pseudophakic children were requiring IOL exchange because of the evolution of high myopic refractive errors.¹⁷⁵

11. Optical correction

Children operated for infantile cataract require optical rehabilitation after surgery. Achieving an optimal visual outcome for the aphakic or pseudophakic child can depend as much on appropriate refractive correction as on the surgery itself.¹⁵¹ Whether a contact lens, IOL, or spectacles are the best option will usually depend on whether an infantile cataract is unilateral or bilateral. For children with unilateral cataracts, a contact lens or IOL is required to give the best visual result with a chance for binocularity.¹²⁸ Children with bilateral cataracts may be managed with contact lenses, intraocular lenses, or aphakic spectacles (Tables 3, 4). All infants will require frequent changes in optical correction to keep their rapidly growing eyes in focus.

Table 3 –

Studies comparing primary intraocular lens implantation versus aphakia following cataract extraction in children < 2 years of age.

Unilateral cataract surgery	Type of study	No of Children	Mean age (range) at surgery (mo)	Mean follow up (years)	Median logMAR VA	Visual axis opacities	Glaucoma + glaucoma suspect
Infant Aphakia Treatment Study (USA)175,180,246 (USA)	Randomized Clinical Trial	110 (IOL n = 55) (50%)	1.8 (1–6)	10.5	Aphakia = 0.86 IOL = 0.89	Aphakia=14% IOL = 68%	Aphakia 47% IOL 36%
IoLunder2 study181 (UK and Ireland)	Prospective observational cohort Study	56 (IOL n = 38) (69%)	2.2 (1–24)	5.0	Aphakia=1.0 IOL = 0.4	Aphakia=11% IOL =40%	Aphakia=45% IOL=11%
Toddler Aphakia and Pseudophakia Treatment Study (TAPS)247 (USA)	Retrospective case series	56 (primary IOL n = 51) (91%)	13.9 (7–24)	4.0	0.80	Aphakia=0% IOL = 18%	Aphakia=20% IOL = 2%
Bilateral Cataract Surgery
IoLunder2 study181 (UK and Ireland)	Prospective observational cohort Study	102 (IOL n = 50) (49%)	3 (1–24)	5.0	0.34	Aphakia=10% IOL = 27%	Aphakia=23% IOL=10%
Toddler Aphakia and Pseudophakia Treatment Study (TAPS)248 (USA)	Retrospective case series	96 (IOL n = 21) (42%)	2.5 (1–7)	4.9	0.35	Aphakia = 8% IOL = 32%	Aphakia = 37% IOL = 10%
Raghudeep Eye Hospital Study179 (India)	Randomized Clinical Trial	54 (IOL n = 29) (54%)	Aphakia = 6.3 IOL=8.1 (1–24)	5.0	Aphakia=0.59 IOL=0.50	Aphakia=8% IOL = 10%	Aphakia=16% IOL=14%
Toddler Aphakia and Pseudophakia Treatment Study (TAPS)272 (USA)	Retrospective case series	40 (IOL n = 27) (68%)	11 (7–24)	4.2	0.18	Aphakia = 0% IOL = 11%	Aphakia = 0% IOL = 4%

Table 4 –

Contact lens correction versus primary IOL implantation after cataract surgery in infants < 7 months of age.

Contact lens correction		Primary intraocular lens implantation
Pros	Cons	Pros	Cons
Pros  • Lower rate of intra/postoperative adverse events  • Lower risk of additional intraocular surgeries	Cons  • Ongoing expense  • Time needed daily to manage contact lenses  • If not worn, risk of severe amblyopia	Pros  • Partial optical correction guaranteed	Cons  • Spectacle overcorrection generally needed  • Higher rate of intra/postoperative adverse events  • Higher risk of additional intraocular surgeries  • Increased parenting stress

The need for a multicenter, randomized clinical trial to answer important questions surrounding pediatric cataract surgery, particularly with regards to infantile intraocular implantation, gave rise to the IATS.²¹¹ The goal of the study was to determine whether contact lens correction or IOL would lead to a better visual outcome after unilateral congenital cataract surgery.¹⁰³ One hundred and fourteen infants 1–6 months of age with unilateral congenital cataracts were randomized to cataract surgery either with or without IOL implantation. If a patient received an IOL, any residual refractive error was corrected with spectacles with the aim of overcorrecting the refractive error by 2.0 D to achieve a near point focus. Similarly, the refractive error of patients left aphakic was corrected with a contact lens with a 2.0 D overcorrection to provide a near point focus. The main outcome measure of the study was grating acuity at 12 months of age and HOTV visual acuity at 4–5 years of age.¹⁹⁵

11.1. Contact lenses

Determining and correcting the refractive error of aphakic infants with contact lens has many inherent challenges. As noted above, patients randomized to contact lens wear in the IATS were fitted with a silicone elastomer or GP contact lens with 2.0 D overcorrection to provide a near-point correction within one week of surgery. If it was not possible to obtain an accurate refraction during the initial week after surgery, a +32 D silicone elastomer contact lens was dispensed with refinement of the power as soon as possible. Guidelines have also been developed for selecting initial contact lens power based on preoperative biometry.²¹² At 2 years of age, the aphakic eye was corrected for emmetropia. Parents were provided with a spare contact lens in case of loss. Children who could not wear one type of contact lens were prescribed the other type and if neither type worked, a custom soft contact lens was fitted. Contact lenses were evaluated at each visit after surgery. Contact lens failure was defined as contact lens wear for less than an average of 4 hours a day for a period of 8 consecutive weeks. After contact lens failure, a trial with aphakic spectacles was mandated before consideration for secondary IOL.¹⁰³

While contact lenses are accepted and commonly used in North America, they are neither available nor is their use advisable in some areas of the world.¹⁰³ Some of the problems inherent with contact lens use include the risk of infection (fungal or bacterial), the difficulty/ challenges of fitting, inserting, and removing lenses in young children for both the eye care professional and the parent, the frequent loss and high cost, which is generally not covered by insurance, and the problem of potential noncompliance leading to dense amblyopia due to correction of refractive error only some of the time.^103,195 IATS investigators reported a high level of contact lens adherence in the IATS likely due to the fact that the lenses were provided at no cost, quarterly telephone interviews assessing contact lens adherence were performed, and strict contact lens failure criteria had to be met before a surgeon could implant a secondary IOL.²¹³ Vasavada et al, however, found the level of contact lens adherence to be much lower—only 6% of patients randomized to contact lens wear wore them for > 1 year.¹⁷⁹

Fifty-four of the 114 IATS participants were randomized to contact lens wear, and all were followed until the age of 5 years.²¹⁴ Forty-six percent of these patients wore silicone elastomer contact lenses, 19% wore GPs, and 29% wore both at some point in time. Thirteen contact lens-related adverse events were described among 7 pts after the first postoperative year, including 2 corneal abrasions, 6 bacterial keratitis episodes, 2 corneal ulcers, and 3 corneal scars following keratitis. All but 1 of the adverse events were related to overnight wear with silicone elastomer lenses. No visually significant sequelae were reported. Of note, during the first 5 years of follow up, only 5% of patients randomized to contact lens wear underwent secondary IOL implantation. While contact lenses were provided at no cost to study participants, the 5- year mean treatment cost for an infant with unilateral congenital cataract treated with contact lenses in this study was $25,331 with supply costs of $7728 compared with mean total costs of $27,090 and supply cost of $3204 in the IOL group.⁷ This is important because these costs (contact lenses, spectacles, patches) are often not covered by insurance. In the study, out of pocket costs were calculated to be twice as high for kids randomized to aphakia and CTL wear compared with primary IOL implantation.⁷ Furthermore, these contact lenses may frequently need to be replaced. Russell and coworkers reported that, on average, children in IATS required 11 silicone elastomer replacement lenses or 17 GPs from infancy to 5 years.²¹⁴

A significant advantage of contact lens wear for these aphakic patients is the possibility of continuous power refinement over time. Lambert and coworkers recently the myopic shift in the aphakic eyes of a cohort of children who underwent unilateral cataract surgery during infancy and were then followed longitudinally for 10.5 years.²¹⁵ The refractive error in aphakic eyes decreased by 44% from infancy to age 10.5 years. About two thirds of children who remained aphakic at age 10.5 continued to wear a contact lens. Furthermore, during years 6–10 follow up after the IATS, many of the children randomized to an intraocular lens were starting to require intraocular lens exchange for high myopia.¹⁷⁵

11.2. Intraocular lenses

Although IOL implantation to address aphakia in children is now common, it is still considered “off label” by the Food and Drug Administration (FDA) in the United States. This designation does not mean that IOL implantation in children is not allowed, only that the IOLs were not tested in children as part of their FDA market approval process in adults.²¹¹

11.2.1. Primary

A major advantage of IOL implantation during surgery for infantile cataract is the ability to provide constant postoperative optical correction for the affected eye. The preferred approach is placement of a 1-piece or 3-piece IOL into the capsular bag. If both haptics of a 1-piece lens cannot not be implanted in the capsular bag, then a 3-piece lens can be implanted into the ciliary sulcus after subtracting 1.0 D from the calculated IOL power (http://www.doctor-hill.com). In young infants, intraocular lens power is calculated preoperatively during the same anesthesia with a targeted postoperative 8 D undercorrection for infants 4–6 weeks and a 6 D undercorrection for infants 6 weeks-6 months.¹⁰³ This recommendation is based on pilot studies and small case series.^216–219 The ultimate goal of IOL selection and for subsequent optical correction with contact lenses or spectacles after surgery is to recognize the importance of near vision in early life, to achieve a small residual myopic error in the pseudophakic eye when a child reaches adulthood, and to try to avoid extreme myopia in the pseudophakic eye necessitating IOL exchange later in life.¹⁰³ IOL power selection can be challenging, though, due to continued ocular growth of the eye of a small child and the difficulty of accurately measuring the biometrics of a child’s eye.²²⁰ Furthermore, standard IOL power calculation formulae are less predictable for children with congenital cataract undergoing IOL implantation in the first 5 years of life.²²¹

Some studies have evaluated the predictability of IOL power calculation formulae only in infant eyes.^{222, 223} Kekunnaya and coworkers evaluated the accuracy of IOL power calculation formulate in 128 eyes of children less than 2 years of age and found the absolute prediction error to be high with all current IOL power calculation formulae but that the SRK II formula was the most predictable.²²³ The IATS results for infants with unilateral cataract showed that the Holladay 1 and SRK/T formulae had the best predictive value.²²² No matter which formula was used, eyes with an axial length less than 18 mm had the most unpredictable results.²²² Vasavada and coworkers evaluated 117 eyes undergoing pediatric cataract surgery with IOL implantation and found that the SRK/T and the Holladay 2 formulas had the least prediction error.²²⁴ This single surgeon study also showed that personalizing the lens formula constant reduced the prediction error significantly for all formulae except the Hoffer Q. In very short eyes (AL<20 mm), the SRK/T and Holladay 2 formulas gave the best prediction error.²²⁴

11.2.2. Polypseudophakia

A single-surgeon 15-year review of 48 eyes of 38 children having piggyback intraocular lens implantation at a mean age of 6.5 months (0.5 months–2.4 years) described early complications in 4 eyes requiring reoperation for intraocular lens tilt, pupillary capture, pupillary block glaucoma, and pupillary membrane.²²⁵ Overall, however, the authors found piggyback intraocular lens implantation to have an acceptable safety profile, with rates of glaucoma comparable to those of infants having cataract surgery without piggyback intraocular lens implantation.²²⁵ Other studies over the past decade, however, have described limitations of polypseudophakia as an approach to optical rehabilitation in infant eyes after cataract surgery. Difficulties in predicting refractive shift after temporary IOL removal in pediatric polypseudophakia have been described.²²⁶ One study from Iran found a higher incidence of reoperation in the setting of piggyback IOLs and no visual benefit compared with aphakia.²²⁷ A 2018 Korean study evaluated the outcomes of 32 eyes undergoing temporary piggyback IOL implantation within the first 3 years of life from 1999 to 2013 and found that, compared with single IOL implantation, these patients had worse visual acuity, required more reoperations, and had a higher risk of secondary glaucoma.²²⁸

11.2.3. Secondary

Secondary IOL implantation in children can be performed at any time after initial cataract extraction for children with infantile cataract. An IOL can be implanted in the ciliary sulcus after all posterior synechiae are severed or in the capsular bag after the Soemmerring ring is opened.¹⁰³ Studies have shown the procedure to be safe and associated with low rates of postoperative complications.^{229, 230} The mean age at time of secondary IOL implantation in one study was 55.2 ± 21.6 months.²²⁹ In this study, 70% of intraocular lenses were implanted into the capsular bag, with 29% in the sulcus and 2% angle-supported.²²⁹ Ultrasound biomicroscopy may be helpful in evaluating the anterior segment of aphakic eyes prior to secondary IOL implantation to evaluate posterior capsular integrity, the ciliary sulcus, anterior chamber depth, corneal thickness, and any other structural changes.²³¹ As secondary IOL implantation may be sought by families of children with a history of poor compliance with contact lens or spectacle wear, it is important to note that secondary IOL implantation will not significantly improve the final visual acuity from that which has already been developed by means of optical rehabilitation and amblyopia therapy.^232,233

11.3. Spectacles

Details of the use of spectacles after surgery for infantile cataract were provided in the protocol for the IATS.¹⁰³ Children in the contact lens group did not receive spectacle correction until 2 years of age. Until that age they were fitted with a silicone elastomer or GP contact lens with 2.0 D overcorrection to provide a near-point correction. At the age of 2 years, these children continue contact lens wear and received spectacles with a D-segment bifocal lens with distance correction for emmetropia and a +3.00 D add. Children in the IOL group received spectacle correction at the time of their 1- month postoperative visit if they had more than 1 diopter of hyperopia, more than 3 diopters of myopia, or more than 1.5 diopter of astigmatism. The overall goal was to correct children younger than 2 years old to −2 D of myopia and children older than 2 years old to emmetropia with a near correction of +3 D. The phakic eye received a plano lens unless hyperopia or myopia > 5 D or astigmatism > 1.5 D or refractive esotropia. Target refraction for the phakic eye was 0-+3 D.¹⁰³

Compliance with spectacle wear may be low, particularly in the youngest patients. A study of Chinese children 3 months to 3 years of age enrolled in the Childhood Cataract Program of the Chinese Ministry of Health showed compliance of 31% in the 3 month to 1 year old group, 78% in the 1–2 year old age group, and 87% in the 2–3 year old age group with presson spherical lenses.²³⁴ In the IATS, spectacle adherence was better in children with 20/40 or better vision in their treated eye and in children with better patching adherence.²³⁵

12. Amblyopia therapy

Congenital cataract is the most common cause of deprivational amblyopia.²³⁶ Removal of a congenital cataract, however, is simply an initial hurdle on the road to optical rehabilitation of an affected eye.²³⁷ Surgery for infantile cataract is most effective when combined with consistent optical correction and diligent amblyopia therapy (Fig. 10).¹⁷⁷ Adherence to patching has been shown to be one of the most important determinants of visual outcome in children with unilateral aphakia or pseudophakia.^103,237

Fig. 10 –

Different outcomes resulting from variations in postoperative management (A) Sixteen-year old diagnosed with a nuclear cataract in her left eye as an infant. She underwent a left lensectomy at age 6 weeks and was fit with a silicone elastomer contact lens postoperatively. Her right eye was patched part-time until age 7 years (1 hour/day/per month of life until age 8 months; 6 hours/day until age 13 months; 5 hours/day until age 2 ½ years; 4 hours/day until age 3 years; 2 hours/day until age 4 years; 4 hours/every other day until age 5 years; 4–5 hours/day twice a week until age 7 years). At 7 years of age, patching was discontinued. Her best-corrected visual acuity was 20/20 in both eyes wearing a +18 D contact lens on her aphakic left eye. She was orthotropic and had 40 s/arc of stereopsis.

(B) Nine-year old diagnosed with a nuclear cataract in his left eye as an infant. He underwent a left lensectomy at age 4 weeks. Postoperatively he wore a silicone elastomer contact lens on his aphakic left eye. His right eye was patched for all but 2 of his waking hours until age 4 years when patching was tapered and then stopped at age 7 years. His visual acuity was 20/20 in both eyes. However, he remained esotropic after one strabismus surgery and he had no stereopsis.

(C) Thirty-five year old woman diagnosed with a congenital cataract in her left eye as an infant. Cataract surgery was deferred until she was age 3 years and no optical correction was prescribed for her aphakia postoperatively. Her best-corrected visual acuity was 20/20 in her right eye and counting fingers in her left eye. She has undergone 4 strabismus surgeries on her left eye.

12.1. Occlusion

An evidence-based protocol for postoperative patching in cases of unilateral infantile cataract surgery was described in detail in the study design of the IATS.¹⁰³ Beginning the second week after cataract surgery, the infant’s unoperated eye was to be patched 1 hour a day per month of life until age 8 months. Subsequently, the phakic eye was patched for 50% of a child’s waking hours. Continued patching was recommended until the patient was at least 6 years of age.¹⁹⁵ Most caregivers were able to patch the prescribed amount in the first 3 months after surgery but family socioeconomic status and parenting stress were determinants of adherence.^238,239 Better adherence to patching during the first 6 months after surgery was associated with better grating acuity at 12 months of age.²⁴⁰ Secondary analysis of the IATS data suggested that similar visual outcomes were achieved with varying amounts of patching, however.²⁴¹ Furthermore, fellow eyes were not adversely affected by intense patching for amblyopia therapy after removal of unilateral infantile cataract and had normal visual outcomes at 10.5 years in the Infant Aphakia Treatment study.²⁴²

12.2. Optical

An opaque or high plus contact lens can be utilized in the phakic eye if patching is unsuccessful. While not specifically studied in the context of aphakia and deprivation amblyopia after surgery for infantile cataract, occlusive contact lenses have been shown to be effective in treating amblyopia in patch intolerant children.^239,240 Patients should be followed closely for potential anterior segment complications and for the recurrence of amblyopia after cessation of therapy.²⁴³

13. Outcomes

13.1. Visual acuity

Total or unilateral cataract, late presentation, presence of nystagmus or strabismus, and suboptimal amblyopia therapy have been identified as predictors of poor visual outcome for children with infantile cataract.^244,245 Visual acuity outcomes for these children must be interpreted carefully in the context of cataract laterality (unilateral or bilateral), aphakic versus pseudophakic status after surgery, and whether the results were observed in a “real-world” context or in the setting of a clinical trial. First, children with bilateral congenital cataracts having timely surgery have better visual outcomes than children with unilateral cataracts,¹⁷⁷ as they are less subject to interocular rivalry and subsequent monocular suppression. Second, visual acuity outcomes from studies conducted in areas of the world in which presentation for infantile cataract surgery is generally delayed are more challenging to interpret as it can be difficult to determine in studies with an older, mixed age cohort whether a cataract was congenital or developmental. Children with some normal period of visual development prior to onset of cataract would be expected to have better visual outcomes as they are less affected by the dense amblyopia experienced by a child who has never had a normal visual experience. Third, visual acuity results from the rigorous confines of clinical trials may reflect benefit to a patient under ideal conditions (efficacy) rather than benefit under usual conditions (effectiveness).¹⁹⁵

A retrospective observational study conducted at a tertiary eye care center in South India found encouraging visual acuity results with primary IOL implantation in children under 6 months of age at the time of surgery. In the bilateral and unilateral cataracts group, 38.7% and 22.2% of eyes, respectively, achieved a BCVA greater than or equal to 20/80 (0.6 logMAR) or better.¹⁸² Mean age at surgery in the bilateral group was 4.6 months. The IoLunder2 prospective observational cohort study conducted in the UK and Ireland reported 5-year outcomes after primary intraocular lens implantation in children less than or equal to 2 years of age at time of surgery for congenital or infantile cataract.¹⁸¹ Of this cohort, 158 of the 254 included children at 31 sites in the United Kingdom and Ireland had bilateral cataracts and 56 had unilateral cataract. The authors reported an overall median visual acuity of 0.34 logMAR (IQR 0.20–0.54) for children with bilateral cataract and 0.70 logMAR (IQR 0.3–1.3) in the operated eye for children with unilateral cataract. Children in either group receiving primary intraocular lens implantation did not have a better visual outcome than those managed with conventional treatment consisting of either aphakic spectacles or CTLs.¹⁸¹ Vasavada and coworkers conducted a randomized, controlled clinical trial of 60 infants who had surgery for bilateral congenital cataract (median age at time of surgery 5.11 months in aphakic group and 6.01 months in pseudophakic group) and reported no difference in mean logMAR visual acuity between bilaterally aphakic and pseudophakic groups of at 5 years after surgery;¹⁷⁹ however, they did note that more patients in the pseudophakic group gave documentable visual acuity using Cardiff acuity cards/Lea Gratings in earlier visits than patients in the aphakic group, indicating that visual rehabilitation was faster in the pseudophakic eyes.¹⁷⁹

The 10.5-year visual acuity outcomes for 110 of the 114 patients with unilateral congenital cataract enrolled in the IATS were presented in 2020.²⁴⁶ Visual acuities outcomes were highly variable in that only 25% achieved excellent visual acuity (logMAR 0.30 [Snellen equivalent 20/40] or better) in their treated eye and 44% had poor vision (logMAR 1.00 [Snellen equivalent, 20/200] or worse) in their treated eye. Visual outcome was not affected positively or negatively by implanting an IOL at the time of cataract extraction. The Toddler Aphakia and Pseudophakia Treatment Study (TAPS) Registry, a retrospective study evaluating outcomes of unilateral cataract surgery in infants 1–7 months of age performed by the IATS investigators during the IATS recruitment period, but outside of the study (2004^–2010), found that visual acuity outcomes in these children were comparable with IATS unilateral outcomes.²⁴⁷ A companion study reviewing outcomes of bilateral cataracts removed in infants 1–7 months of age using the TAPS registry found that visual acuity in the better-seeing eye after bilateral cataract surgery in infants younger than 7 months of age is good (20/45; logMAR range 0.00–1.18) in both aphakic and pseudophakic children.²⁴⁸

Studies involving older children operated for congenital cataracts have also shown visual improvement. In the Miraj Pediatric Cataract Study III conducted in India, only 14% of 258 patients with bilateral congenital and developmental cataracts were operated between 0 and 2 years, but the results showed that >6/60 (logMAR 1.00; Snellen 20/200) visual acuity outcomes are possible in nearly half (44%) of children operated for bilateral congenital cataract even in relatively resource poor settings.²⁴⁹ Yangzes and coworkers conducted a retrospective chart review of 93 children having IOL placement for unilateral congenital cataract within the first 4 years of life (mean age at surgery was 13.23 ± 11.89 months; mean follow up period 24.37 ± 17.35 months) and found that mean visual acuity was 0.79 ± 0.11 logMAR.²⁴⁵ A total of 60.7% of these children (n = 31) had a best corrected visual acuity of 20/80 or better.²⁴⁵ A small retrospective interventional Brazilian case series of 14 microphthalmic eyes (mean ocular axial length 19.2 ± 0.9 mm) undergoing congenital cataract surgery in children < 4 years of age (mean age at time of surgery 21.7 ± 2.9 months) showed that primary intraocular lens implantation could result in significant best-corrected visual acuity improvement (pre- vs. postoperative best-corrected visual acuity 2.09 ± 0.97 logMAR and 0.38 ± 0.08 logMAR in bilateral cases and 1.83 ± 1.04 logMAR and 0.42 ± 0.13 logMAR in unilateral cases, respectively) even in these smaller eyes.²⁵⁰

13.2. Visual outcomes after secondary intraocular lens implantation

Shenoy and coworkers evaluated visual outcome of 174 aphakic eyes of patients in Hyderabad, India, with a history of either unilateral or bilateral congenital cataract after secondary IOL implantation at a mean age of 6.08 ± 3.75 years with a mean follow up of 2 years (minimum 3 months).²⁵¹ The authors reported a mean best-corrected visual acuity improvement from 1.08 ± 0.65 in aphakic children to 0.55 ± 0.51 logarithm of the minimal angle of resolution in pseudophakic children. Overall, 35% of eyes in the bilateral group attained a final best-corrected visual acuity of 20/40 (0.3 logarithm of the minimal angle of resolution) or better, whereas only 2 eyes (8.7%) in the unilateral group attained a final best-corrected visual acuity of 20/40 (0.3 logarithm of the minimal angle of resolution) or better. Kim and coworkers in Korea found a similar level of success in 37 patients with dense, bilateral, congenital cataracts who utilized aphakic correction with glasses followed by secondary intraocular lens implantation around age 2 years, with 44% of these children attaining 20/40 BCVA during a mean follow up period of 81.4 months.²⁵²

The median age at IOL surgery for the 24/55 patients randomized to aphakia with contact lens correction who had secondary IOL surgery later in the IATS was 5.4 years.²⁵³ While visual outcomes at 10.5 years were similar for the eyes having secondary IOL placement and the eyes remaining aphakic, the mean refraction for eyes having IOL implantation after the 4.5 year study visit was −3.2 ± 2.7D compared with −5.5 ± 6.6D in eyes with primary IOL.²⁵³ Interestingly, many children (56% of those) randomized to contact lenses in the IATS who were anticipated to have secondary intraocular lenses placed during childhood in fact remained aphakic and wearing a contact lens at 10.5 years. This group actually had a better median visual acuity (20/47) than all other subgroups.²⁴² For these patients, secondary intraocular lens placement can be considered at any point later in life with an excellent expected outcome.²⁴²

13.3. Stereopsis

Hartmann and coworkers assessed stereopsis results at 4.5 years of age in the IATS and found that 25% of all pts had a positive response to at least 1 of the tests (Frisby, Randot Preschool, and Titmus Fly) administered by a masked examiner.²⁵⁴ There was no difference between the contact lens group and the intraocular lens group, but the median age at surgery was younger (1.2 vs. 2.4 months) and median visual acuity was better (20/40 vs. 20/252) for patients with stereoacuity than for those without stereopsis.²⁵⁴ Early surgery and presence of visual acuity better than 20/40 appeared to be more important than type of initial optical correction used for development of stereopsis.²⁵⁴

13.4. Strabismus

Strabismus is common in patients who have had surgery for infantile cataract. Tartarella and coworkers reported that, of 117 patients having surgery for congenital cataract, 34% had esotropia, 21% had exotropia, while 44% were orthophoric.⁸⁵ Ocular misalignment was noted in 17.5% of the infants at time of presentation in the Negalur et al study in India, with nystagmus in 42.5%. Four children (10%) underwent strabismus surgery following cataract extraction. At final visit in the same study, 40% had some form of ocular misalignment (esotropia, exotropia, or dissociated vertical deviation).¹⁸² At one year in the IATS, 67% of pseudophakic infants and 75% of aphakic infants developed strabismus.²⁵⁵ Interestingly, the younger cohort (<49 days) at time of surgery demonstrated less strabismus (58%) than the older cohort (49 days, 80%).²⁵⁵ Nystagmus and related fixation instabilities were also found in 60% of children who had interpretable recordings in both the contact lens group and the intraocular lens group in the IATS.²⁵⁶ Fusion maldevelopment nystagmus is found in many children with a history of congenital cataract and it is strongly associated with the infantile onset of binocular discordant input.^257–259

13.5. Reading performance

Because reading relies on oculomotor function, specifically sequential saccades, it is conceivable that the binocularly disruptive influence of a unilateral infantile cataract could disrupt a child’s ability to learn to read.²⁵⁷ Kelly and coworkers in 2020 found, however, that children who had undergone surgery for a dense, unilateral cataract did not have a reading rate different from that of controls.²⁵⁷

13.6. Motor skills

Celano and coworkers evaluated motor skills of children aged 4 years 6 months enrolled in the IATS with the Movement Assessment Battery for Children, Second Edition (MABC-2) and found that children with unilateral congenital cataract may have delayed motor functioning at 4 years 6 months that could adversely affect their social and academic functioning.²⁶⁰

13.7. Central corneal thickness, endothelial cell count, and corneal biomechanical properties

Central corneal thickness (CCT) increases in eyes undergoing congenital cataract surgery have been noted, particularly for children having surgery between 0 and 1 year of age.²⁶¹ Investigators found that the mean CCT change at 3 years was 70.11 ± 42.3 microns for children having surgery between 0 and 1 years of age, compared with smaller changes after surgery in older age groups. Intraocular pressure was not correlated to CCT change.²⁶¹ Changes in endothelial cell count have only been reported for older pediatric patients (mean age at surgery 8.8 years ± 2.7 years (range 4–15 years) after cataract surgery.²⁶² Mean endothelial cell loss was 1.95% at POM #1 and 5.05% at POM #6.²⁶² Simsek and coworkers evaluated corneal biomechanical properties using ocular response analyzer to examine aphakic and pseudophakic patients after congenital cataract surgery (compared to an age- and sex-matched control group) and found that CCT increased, but that corneal hysteresis and corneal resistance factor were not affected by surgery.²⁶³

13.8. Progressive myopia

Significant myopic shift has been noted following IOL implantation in the youngest patients. Negalur and coworkers reported long-term outcomes following primary IOL implantation in 69 eyes of 38 infants younger than 6 months at a tertiary eye care center in South India and observed a large myopic shift (average 6.7 diopters over 4.2 years) over a mean follow up period of 51 months.¹⁸² The myopic shift was greater in eyes of patients with unilateral cataracts than in bilateral cases.¹⁸² At 10.5 years after randomization to the aphakic arm in the IATS, refractive error in the aphakic eyes had decreased by 44%.²¹⁵ Furthermore, at 6–10 years during the study follow up period, a growing number of pseudophakic children were requiring IOL exchange because of the development of highly myopic refractive errors.¹⁷⁵ The high myopia resulting from early surgery for infantile cataract is attributed to only a modest reduction in axial elongation after cataract surgery—less than what was expected based on animal studies–and the fixed position of the IOL in the eye that, in conjunction with the axial elongation, magnifies the myopic shift that occurs with axial growth.²²⁰ Investigators have concluded that the targeted refractive error in young children having an IOL implanted should be aimed at undercorrection in anticipation of a future myopic shift.²²⁰

14. Conclusions

More effective early screening in all settings and better epidemiologic data from resource-poor settings is needed to determine the true burden of infantile cataracts and determine how barriers such as delayed presentation can be addressed to improve visual outcomes. Strategies for managing congenital cataracts must be adapted and developed according to regional conditions. A framework for acceptable outcomes must focus on developing systems to address the critical components of education, access, quality care, and good followup.^{18,20,21,26,28,39,46,264–267} Studies on follow-up patterns and associated risk factors in the setting of pediatric cataract surgery are important as they pinpoint factors associated with poor follow up and suggest potential interventions.³⁷ Practice patterns with regards to management of infantile cataracts continue to evolve. Multiple studies have shown definitive visual benefit associated with early detection and early cataract surgery. Surgery alone for infantile cataract will not be successful without appropriate and timely optical rehabilitation and close monitoring for strabismus, amblyopia, and glaucoma. The longterm risks of glaucoma and progressive myopia in patients undergoing infantile cataract surgery with or without IOL implantation are gradually being elucidated over time. Continued efforts to define quality of life for children and adults affected by congenital cataracts using specific vision-related quality of life measures are in order.⁴ We must strive for the continued evolution of strategies and technologies with the potential to further improve outcomes of surgery for infantile cataract.

14.1. Literature search

A PubMed search was conducted for all articles with the key term “infantile cataract” or “congenital cataract.” While select articles published before 2010 are included for historical purposes, the review is based mainly on articles published in the past decade. Owing to the large number of articles retrieved, articles selected focused on clinical trials, review articles, or were reports containing new information about the characteristics, diagnosis, or management of infantile cataracts. A limitation of the study is that articles in languages other than English were excluded. Studies based on surveys or questionnaires were generally excluded as were single case reports.