Journal of Pediatric Ophthalmology and Strabismus

Original Article Supplemental Data

Cortical Visual Impairment in Congenital Cytomegalovirus Infection

Haoxing Douglas Jin, MD; Gail J. Demmler-Harrison, MD; Jerry Miller, MS, PhD; Jane C. Edmond, MD; David K. Coats, MD; Evelyn A. Paysse, MD; Amit R. Bhatt, MD; Kimberly G. Yen, MD; Joseph T. Klingen, MD; Paul Steinkuller, MD; for The Congenital CMV Longitudinal Group

Abstract

Purpose:

To describe the presentation, evolution, and long-term outcome of cortical visual impairment (CVI) in patients with symptomatic congenital cytomegalovirus (CMV) infection, and to identify risk factors for the development of CVI in patients with symptomatic congenital CMV.

Methods:

Retrospective subanalysis of a long-term prospective cohort study with data gathered from 1982 to 2013.

Results:

Eleven of 77 (14.3%) patients with symptomatic CMV, 0 of 109 with asymptomatic CMV, and 51 control patients had CVI. Overall, patients with symptomatic CMV had worse vision than patients with asymptomatic CMV, who in turn had worse vision than control patients. Microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, and neonatal onset of sensorineural hearing loss were risk factors associated with CVI.

Conclusions:

CVI may result from symptomatic congenital CMV infection. The relationship of CVI and its risk factors in patients with CMV suggests the potential to predict the development of CVI through predictive modeling in future research. Early screening of CVI in children born with symptomatic congenital CMV can facilitate educational, social, and developmental interventions.

[J Pediatr Ophthalmol Strabismus. 2019;56(3):194–202.]

Abstract

Purpose:

To describe the presentation, evolution, and long-term outcome of cortical visual impairment (CVI) in patients with symptomatic congenital cytomegalovirus (CMV) infection, and to identify risk factors for the development of CVI in patients with symptomatic congenital CMV.

Methods:

Retrospective subanalysis of a long-term prospective cohort study with data gathered from 1982 to 2013.

Results:

Eleven of 77 (14.3%) patients with symptomatic CMV, 0 of 109 with asymptomatic CMV, and 51 control patients had CVI. Overall, patients with symptomatic CMV had worse vision than patients with asymptomatic CMV, who in turn had worse vision than control patients. Microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, and neonatal onset of sensorineural hearing loss were risk factors associated with CVI.

Conclusions:

CVI may result from symptomatic congenital CMV infection. The relationship of CVI and its risk factors in patients with CMV suggests the potential to predict the development of CVI through predictive modeling in future research. Early screening of CVI in children born with symptomatic congenital CMV can facilitate educational, social, and developmental interventions.

[J Pediatr Ophthalmol Strabismus. 2019;56(3):194–202.]

Introduction

Cortical visual impairment (CVI) is the most common cause of visual impairment in children in the developed world.1 It is characterized by visual impairment or impaired functionality in performing vision-guided tasks due to damage to the central nervous system (CNS) that does not involve the ocular structures.2,3 It is most commonly caused by perinatal or postnatal injuries to the developing brain by insults such as brain malformation, hypoxia/ischemia, prematurity, trauma, infection, ventriculo-peritoneal shunt blockage, drugs, and certain neurological diseases.1,3–5 Patients diagnosed as having CVI often experience severe central vision loss, despite having otherwise normal eye examinations.6 Reports on intrauterine infection as potential causes of CVI are scarce.7

The World Health Organization estimates 39 million people are blind and 246 million are visually impaired worldwide.8 Children younger than 14 years make up 3.6% (1.42 million) of the total blind and 7.7% (18.9 million) of the visually impaired populations.8 In the United States, CVI, retinopathy of prematurity (ROP), and optic nerve hypoplasia/atrophy have been found to be the top three causes of blindness and visual impairment in children.9–12 It is estimated that 23.6% of all childhood blindness is caused by CVI.12

Cytomegalovirus (CMV) is the most common congenital viral infection in the United States, affecting approximately 0.5% to 1% (approximately 40,000) of all live births annually.13 It is transmitted transplacentally from the pregnant mother to the unborn child via primary infection or viral reactivation. Approximately 10% to 15% of newborns with congenital CMV infection will have one or more signs (eg, jaundice, hepatosplenomegaly, low birth weight, microcephaly, seizure, purpura, or chorioretinitis) at birth, and thus are classified as having symptomatic infection, with the remaining newborns having no signs or symptoms at birth and classified as asymptomatic.13 Congenital CMV infection is known to cause ophthalmologic, audiologic, and other neurodevelopmental sequelae in patients.14–16 Most of the publications on vision and congenital CMV infection focus on the ocular sequelae, such as chorioretinitis, optic nerve atrophy, and strabismus. There has been a limited investigation on CVI and congenital CMV infection.14,15,17 Although CVI is known to occur among patients with symptomatic congenital CMV, there is no method to accurately predict which patients will develop CVI at birth. The presentation, evolution, risk factors, and long-term outcome of CVI in congenital CMV infection have not been fully described. Because each child with CVI may present differently, management should be fitted to each child's unique functional status; furthermore, early detection of CVI in patients with congenital CMV allows timely intervention to maximize functional vision over time.

Patients and Methods

The purpose of this study was to describe the presentation, evolution, and long-term outcome of CVI in patients with symptomatic congenital CMV infection, and to identify risk factors for the development of CVI in patients with symptomatic congenital CMV.

The Houston Congenital CMV Longitudinal Study is a prospective, multidisciplinary cohort study conducted since 1982 with a total of 237 children enrolled, of which 77 were categorized as symptomatic at birth, 109 were asymptomatic at birth, and 51 were uninfected controls.18 The current study is a post hoc retrospective analysis of The Houston Congenital CMV Longitudinal Study. This study was approved by the institutional review board of Baylor College of Medicine and conformed to the requirements of the Health Insurance Portability and Accountability Act of 1996. Informed consent was obtained from human participants.

Patients in the study cohort received serial age-appropriate ophthalmologic examinations at follow-up study examinations. Best corrected visual acuity (BCVA) was classified as normal, moderate impairment, or severe impairment. Normal BCVA was defined as 20/40 or better on optotype visual acuity testing in each eye for patients who were able to cooperate, or fixing on and following a near object for nonverbal and preverbal children. Moderate visual impairment was defined as BCVA of 20/200 or better, BCVA of 20/40 or worse, or the presence of fixation on a near object but no following. Severe impairment was defined as BCVA of 20/200 or worse, no demonstrable fix or follow behavior, or no reaction to light.

CVI is a severe form of vision loss that is primarily caused by damage to the posterior visual pathways of the central nervous system, with reduced BCVA as a result of a disease process that does not primarily involve the ocular structures.3,19

The diagnosis of CVI was made clinically in study patients when they had an otherwise normal eye examination, yet showed abnormal visual responses, including difficulty to fix and follow purposefully, or when the examination findings, such as small peripheral retinal lesions, could not explain the degree of visual impairment. CVI was further confirmed by visual evoked responses in one of the patients. Neurological imaging studies were also reviewed when available.

A retrospective review of clinical records identified 11 patients diagnosed as having CVI. Patient records were analyzed and each patient's presentation, clinical course, clinical correlations, and long-term outcome were described. Demographics, birth characteristics, and ocular findings are described in patients with CVI and compared to patients with non-symptomatic CVI in the study cohort.

Statistical analysis employed chi-square or Fisher's exact tests when comparing categorical variables and t tests when comparing continuous variables. Risk factors were assessed using regression models to determine their association with the future development of CVI. Various characteristics found at birth and before the CVI diagnosis were entered into univariate logistic regressions to assess the strength and significance of these risk factors for the development of CVI. Multivariate logistic regression models were developed using some of these variables in combination to predict CVI in individual cases. The logistic regression procedure normally predicts the probability of each patient having the outcome of interest (CVI) from 0 to 1, with 0.5 as the default (ie, if the prediction is 0.5 or higher, then the outcome is predicted to occur; if the prediction is below 0.5, then it is predicted to not occur). In our models, we adjusted the cutoff level to identify more possible cases of CVI, albeit at the cost of identifying more false-positives results along with them. By using the predicted versus the actual number of CVI cases identified in each multivariate model, the sensitivity, specificity, false-positive rate, false-negative rate, positive and negative predictive values, and overall performance of each model were calculated.

Results

There were 11 patients who developed CVI, and all were in the group who were symptomatic at birth (11 of 77 [14.3%]). Comparisons were made between these 11 patients and the remaining 66 symptomatic patients who did not develop CVI. Demographic and clinical information are summarized in Table 1. There were no significant differences between gender, race/ethnicity, gestational age, and ganciclovir treatment status. The average birth weight was lower in patients with CVI than in patients without, but it did not reach statistical significance (P = .069). The mean number of eye examinations was 10.3 (range: 2 to 21) for the 11 patients with CVI compared with 7.1 (range: 0 to 19) for the patients with symptomatic congenital CMV (P = .058) (Table 1). The mean age at CVI diagnosis was 3.3 years (range: 11 months to 9.9 years) (Table 2).

Demographic Data of Patients in the Current Study (N = 77)a

Table 1:

Demographic Data of Patients in the Current Study (N = 77)

Ocular and Visual Findings (N = 77)a

Table 2:

Ocular and Visual Findings (N = 77)

Table 2 shows the significance of the differences in rates of visual impairment between patients with and without symptomatic CVI, with 36.4% versus 3% having moderate impairment (P = .003) and 63.6% versus 4.5% having severe impairment (P < .001). Seventy-seven percent of the patients without symptomatic CVI had normal vision (P < .001). Ocular abnormalities were more common among patients with CVI than those without, including optic atrophy (36.4% vs 7.6%, P = .020), chorioretinitis/retinal scars (54.5% vs 19.7%, P = .022), strabismus (63.6% vs 16.7%, P =.002), and nystagmus (45.5% vs 9.1%, P = .007) (Table 2). No significant changes were observed in visual acuity, including fix and follow behavior over the study period in patients with CVI.

Nonophthalmologic sequelae were also observed in patients with symptomatic CVI. Sensorineural hearing loss (SNHL) occurred in all 11 (100%) patients with CVI and in 46 (69.7%) patients without symptomatic CVI (P = .057). There were no differences in the age of diagnosis or the laterality for the hearing loss. SNHL occurred in the neonatal period in 7 (63.6%) of 11 patients with CVI versus 20 (30.3%) patients without symptomatic CVI (P = .229). In 52 symptomatic patients, SNHL was severe enough to require hearing devices (37 hearing aids and 15 cochlear implants). Seven of 11 patients with CVI required hearing aids but no patients underwent cochlear implantation. Among the other birth characteristics for symptomatic patients, there was high statistical significance for microcephaly (Olsen 3rd percentile)20 (P = .001), white matter abnormality (P = .004), seizure at birth (P = .019), intracranial calcifications (P = .019), encephalomalacia (P = .002), and dilatation of ventricles (P = .020), which all occurred more frequently in patients with CVI than without (Table 3).

Nonophthalmologic Sequelae and Comorbidities (N = 77)a

Table 3:

Nonophthalmologic Sequelae and Comorbidities (N = 77)

Five predictive models based on 11 variables were created using logistic regression to predict which symptomatic patients would have developed CVI (Tables 45). Model 5 showed the variables of microcephaly, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, intracranial calcifications, neonatal hearing loss, and severe visual impairment were predictors of CVI. Furthermore, model 5 had the most desirable parameters of any predictive model. This model correctly identified 10 of 11 cases of CVI that occurred, giving the lowest false-positive rate (23.1%), high sensitivity (90.9%) and specificity (95.5%), and high negative predictive value (98.4%) for CVI (Table 5). Model 3 also had good overall performance characters. If not all variables were known, then model 1, which used presence of microcephaly at birth as the only parameter, performed well as a predictive risk factor for CVI with high sensitivity and reasonably good specificity (Table 5).

Logistic Regressions of CVI Risk Factors and Predictive Modeling

Table 4:

Logistic Regressions of CVI Risk Factors and Predictive Modeling

CVI Predictive Performance Characteristics of Selected Models (N = 77)

Table 5:

CVI Predictive Performance Characteristics of Selected Models (N = 77)

Discussion

It is widely known from the literature that congenital CMV infection can cause long-lasting visual sequelae such as optic atrophy and chorioretinitis.13–18 The 11 patients with CVI in our study were symptomatic at birth by having one or more clinical symptoms of congenital CMV infection. In clinical settings, 10% to 15% of patients who are congenitally infected with CMV show symptoms at birth,21 whereas the remaining 85% to 90% are asymptomatic at birth. Despite few reports of CVI in congenital CMV infection in the literature, our findings support that CVI cases are observed frequently in symptomatic congenital CMV infection.14,15,17 In comparison, the 109 children born with asymptomatic congenital CMV infection and the 51 uninfected controls did not develop CVI during the study period of observation.

Prematurity is a known major risk factor for CVI. Optic radiations are supplied with blood from the germinal matrix, and in premature infants, the germinal matrix is a watershed area of the brain that is prone to hypoxic, ischemic, and hemorrhagic insults,1 thus causing CVI. In our study, there were no significant differences in prematurity or gestational ages in the group of patients with and without symptomatic CVI (Table 3). This finding suggests that, although symptomatic congenital CMV can be associated with premature birth, something in addition to prematurity must be contributing to the development of CVI, such as direct viral interference with neurogenesis. The high tropism of CMV for infecting CNS cell lines is evident from the predominance of CNS abnormalities (eg, microcephaly, white matter abnormality, or encephalomalacia) observed in the setting of symptomatic congenital infection, yet the precise neurodevelopmental pathway and cellular targets of infection remain incompletely characterized.21 Reports have shown intravenous ganciclovir and oral valganciclovir can improve the audiologic and neurodevelopmental outcomes of symptomatic neonates.22 However, Kimberlin et al.22 did not report visual outcomes, and ganciclovir treatment was not associated with fewer occurences of CVI or improved vision in the patients with symptomatic congenital CMV infection and neurologic involvement in our study.

We found that CVI often resulted in severe visual impairment in patients with symptomatic CMV. Common ocular comorbidities include optic nerve atrophy, chorioretinitis/retinal scars, strabismus, and nystagmus. The timing of acquiring congenital CMV infection is connected to the level of a child's disability.23 In the current study, patients diagnosed as having CVI had on average four times more ocular findings compared to patients without CVI. Therefore, we suspect these patients acquired infection earlier in utero than those without CVI. Children with CVI resulting from trauma or hypoxic-ischemic injuries tend to have gradual and partial recovery of their vision4,24; however, there is no clear evidence that our patients with CVI with symptomatic congenital CMV experienced measurable changes in visual acuity or functional fix and follow behavior over time. Nevertheless, it is important to be aware that the patients with CVI in our study also had multiple other visual, ocular, and neurodevelopmental sequelae from congenital CMV infection, which could have masked improvement in CVI.

In addition to ocular and visual comorbidities, symptomatic congenital CMV infection causes severe neurodevelopmental and sensorineural sequelae. Sensorineural hearing loss, microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia (leukomalacia), and seizures at birth were all associated with the presence of CVI. Taking these risk factors into account, a predictive model could help to screen patients with congenital CMV who are at risk for CVI, which can aid clinicians, parents, and educators to take preemptive steps toward early intervention and rehabilitation.

There were some limitations with predictive modeling. First, our current predictive modeling assumed the presence of the predictors to have occurred before and not after the diagnosis of CVI, but in actual practice CVI was diagnosed concurrently with certain model variables at the same evaluation visit for some patients. The mean age at CVI diagnosis was 3.3 years (range: 11 months to 9 years); therefore, although not guaranteed, it would be reasonable to assume that the predictors had occurred prior to CVI diagnosis. Second, our sample size was small. Developing models from larger or pooled populations of symptomatic patients would be desirable. Finally, although birth characteristics such as microcephaly would likely be known for other patients with symptomatic CMV, we assessed other characteristics (ie, intracranial calcification) that might not be identified in patients not included in the study. This could limit the applicability of a predictive model that relies on knowing the presence or absence of detailed visual and non-visual findings from serial examinations or neuroimaging. Despite these limitations, logistic regression-based predictive models have potential applicability in clinical medicine. Evidence-based predictive models could become useful precision medicine tools for patients with symptomatic congenital CMV, who are known to be at risk for CVI.

To help children with CVI, ophthalmologists first have to correctly identify this condition. Although logistic regression-based predictive modeling is not a diagnostic tool, it could be developed into a screening instrument or clinical decision support tool to help identify cases that may require heightened medical surveillance. A thorough clinical examination of the visual system should follow, and is often sufficient to diagnose CVI. However, in equivocal cases, visual evoked potentials and brain imaging can offer additional confirmation.24

CVI can affect many aspects of vision, including visual acuity, visual fields, color vision, contrast sensitivity, perception of movement, ability to see details in complex visual scenes, visual memory formation, and recognizing the significance of facial expression.25,26 When diagnosing CVI, clinicians should further specify which aspects of visual functions are affected in the child. Examples of functional vision testing include visually guided motor response, attentive gaze, visual recognition of objects, pictures, and faces, preferences for moving versus static stimuli, preferences for familiar versus novel stimuli, and suppression of visual responses by auditory or tactual simulation.25,26 In 2006, Roman-Lantz developed the CVI Range, which is a reliable functional vision assessment tool for children with CVI.6,27 Detailed descriptions of visual function impairment help target specific rehabilitation planning, the intervention of CVI should be tailored to each child's unique functional status, and management goals should focus on early intervention and collaboration with parents, educators, and other health care providers to maximize functional vision over time. Future larger-scale studies focusing on predictive models, functional vision progress, rehabilitation methods, and educational accommodation for children with congenital CMV and CVI are needed.

Conclusion

CVI may be suspected when one or more more classic CMV symptoms present at birth. Microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, and neonatal onset of sensorineural hearing loss are risk factors for CVI. The relationship between CVI and its risk factors suggests it is possible to predict the development of CVI through predictive modeling in future research. Early screening for CVI in children born with symptomatic congenital CMV can help with early educational, social, and developmental intervention.

References

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Demographic Data of Patients in the Current Study (N = 77)a

CharacteristicSymptomatic CMV With CVI (n = 11)Symptomatic CMV Without CVI (n = 66)P
Male6 (54.5%)30 (45.5%).576
African American2 (18.2%)10 (15.2%).678
Asian0 (0%)2 (3.0%)1.000
White9 (81.8%)54 (81.8%).640
  Hispanic2 (18.2%)17 (25.8%).722
  Non-Hispanic9 (81.8%)49 (74.2%)
Mother's age (y), mean ± SD24.3 ± 8.123.7 ± 6.6.795
GA (weeks), mean ± SD36.9 ± 2.137.5 ± 2.2.417
Birth weight (g), mean ± SD2,073.0 ± 532.62,448.6 ± 637.8.069
Cesarean section birth3 (27.3%)30 (45.5%).214
Vaginal birth8 (72.7%)36 (54.5%)
Age at most recent examination (y), mean ± SD (range)11.0 ± 6.5 (2 to 21.1)12.2 ± 8.0 (2.4 to 27.3).647
Avg. no. of eye examinations, mean ± SD (range)10.3 ± 6.4 (2 to 21)7.1 ± 4.9 (0 to 19).058
Ganciclovir treatment5 (45.5%)13 (19.7%).116

Ocular and Visual Findings (N = 77)a

CharacteristicSymptomatic CMV With CVI (n = 11)Symptomatic CMV Without CVI (n = 66)P
Percent (%) of total patients14%86%
Age at CVI diagnosis (y), mean ± SD (range)3.3 ± 3.0 (11 to 9.9)
Vision at most recent examination
  Normal0 (0%)51 (77.3%)< .001
  Moderate impairment4 (36.4%)2 (3.0%).003
  Severe impairment7 (63.6%)3 (4.5%)< .001
  Not evaluated0 (0%)10 (15.2%).341
Optic atrophy4 (36.4%)5 (7.6%).020
  Unilateral1 (25%)1 (20%)
  Bilateral2 (50%)2 (40%)
  Laterality not recorded1 (25%)2 (40%)
Chorioretinitis or retinal scars6 (54.5%)13 (19.7%).022
  Unilateral2 (33.3%)7 (53.8%)
  Bilateral2 (33.3%)5 (38.5%)
  Not noted2 (33.3%)1 (7.7%)
  Retinal detachment0 (0%)2 (3.0%)1.000
Strabismus7 (63.6%)11 (16.7%).002
  Esotropia0 (0%)3 (27.3%).245
  Exotropia7 (100%)8 (72.7%)
Amblyopia0 (0%)3 (4.5%)1.000
Anterior segment abnormality1 (9.1%)4 (6.1%).548
Nystagmus5 (45.5%)6 (9.1%).007
Astigmatism5 (45.5%)17 (25.8%).227
Cupping2 (18.2%)3 (4.5%).146
Vitreous hemorrhage0 (0%)7 (10.6%).584
Cataract1 (9.1%)1 (1.5%).267
Ocular abnormalities, mean ± SDb4.1 ± 1.71.0 ± 1.4< .001

Nonophthalmologic Sequelae and Comorbidities (N = 77)a

CharacteristicSymptomatic CMV With CVI (n = 11)Symptomatic CMV Without CVI (n = 66)P
SNHL11 (100%)46 (69.7%).057
  Unilateral1 (9.1%)10 (21.7%).672
  Bilateral10 (90.9%)36 (78.3%)
  Neonatal onsetb7 (63.6%)20 (43.5%).229
  Onset after 28 days4 (36.4%)26 (56.5%)
  Congenital onsetc8 (72.7)25 (54.3%).326
  Delayed onsetd3 (27.3%)21 (45.7%)
Age at SNHL diagnosis (y), mean ± SD (range)0.67 ± 1.78 (birth to 6 y)1.14 ± 2.58 (birth to 11 y).566
Hearing aid7 (63.6%)30 (45.5%).264
Cochlear implant0 (0%)15 (22.7%).109
SGA6 (54.5%)22 (33.3%).194
Prematurity4 (36.4%)20 (30.3%).732
Petechiae9 (81.8%)46 (69.7%).334
Anemia0 (0%)3 (4.5%).626
Splenomegaly5 (45.5%)34 (51.5%).481
Hepatomegaly4 (36.4%)40 (60.6%).120
Jaundice3 (27.3%)27 (40.9%).306
Bilirubin > 3 mg/dL2 (18.2%)26 (39.4%).193
Platelets < 75/mm35 (45.5%)45 (68.2%).080
ALT > 100 IU1 (9.1%)11 (16.7%).676
Neonatal pneumonia0 (0%)2 (3.0%).733
Microcephalye9 (81.8%)16 (25.4%).001
Seizure at birth3 (27.3%)2 (3.0%).019
Neurological abnormality6 (54.5%)17 (25.85%).061
Abnormal head CT results11 (100.0%)52 (78.8%).194
Intracranial calcifications10 (90.9%)33 (50.0%).019
Dilatation of ventricles9 (81.8%)28 (42.4%).020
Gray matter abnormality1 (9.1%)2 (0.9%).133
White matter abnormality6 (54.1%)34 (15.0%).004
Cerebral immaturity3 (27.3%)20 (8.8%).079
Encephalomalacia3 (27.3%)4 (1.8%).002

Logistic Regressions of CVI Risk Factors and Predictive Modeling

Variable No.Univariate Logistic Regressions Variable DescriptionORLCLUCLPCutoff
1Microcephaly (Olsen 3rd percentile)12.972.5466.10.0020.5
2Seizures at birth12.001.7383.03.0120.5
3Optic atrophy before CVI2.710.4616.12.2730.5
4Chorioretinitis/retinal scar before CVI2.330.599.17.2260.5
5Strabismus before CVI6.001.5523.19.0090.5
6Intracranial calcification at birth10.001.2182.61.0330.5
7Nystagmus before CVI1.000.119.211.0000.5
8Neonatal hearing loss4.031.0615.30.0410.5
9Severe vision impairment before CVI> 1,5000.00a.9990.5
10Encephalomalacia at birth5.811.1030.82.0390.5
11Leukomalacia at birth1.550.1615.32.7080.5

CVI Predictive Performance Characteristics of Selected Models (N = 77)

ModelVariableaSensitivitybSpecificitycFalse-Positive RatedFalse-Negative RateePV+fPV-gCutoffCorrectly ClassifiedOverall Performanceh

Patients With CVI (n = 11)Patients Without CVI (n = 66)
Model 1181.8%74.2%65.4%3.9%34.6%96.1%0.294975.3%
Model 21, 2, and 381.8%72.7%66.7%4.0%33.3%96.0%0.294874.0%
Model 31, 2, 3, 5, 6, 8, and 981.8%95.5%25.0%3.1%75.0%96.9%0.396393.5%
Model 41, 2, 3, 5, 6, 8, and 990.9%87.9%44.4%1.7%55.6%98.3%0.2105888.3%
Model 51, 2, 3, 4, 5, 6, 8, and 990.9%95.5%23.1%1.6%76.9%98.4%0.2106394.8%

The Congenital CMV Longitudinal Study Group Members

Amit R. Bhatt, MDSara Reis, RN
Peggy Blum, AuDAnn Reynolds, MD
Frank Brown, MDJudith Rozelle, MS
Francis Catlin, MDSherry Sellers Vinson, MD
Alison C. Caviness, MD, PhD, MPHO'Brien Smith, PhD
David K. Coats, MDPaul Steinkuller, MD
Jane C. Edmond MDMarie Turcich, MS
Daniel Franklin, MDJohn Voigt, MD
Jewel GreerBethann Walmus
Carol Griesser, RNDaniel Williamson, MD
Mohamed A. Hussein, MDKimberly G. Yen, MD
Isabella Iovino, PhDMartha D. Yow, MD
Allison Istas, MPHTexas Children's Hospital Audiology
Mary K. Kelinske, ODShahzad Ahmed, MD
Antone Laurente, PhDHanna Baer, MD
Thomas Littman, PhDGail J. Demmler-Harrison, MD
Jerry Miller, PhDMarily Flores, MS
Mary Murphy, MSCindy Gandaria
Christopher Nelson, MDHaoxing Douglas Jin, MD
Daniel Noyola, MDJoseph T. Klingen, MD
Evelyn A. Paysse, MDJill Williams, MA
Alan Percy, MD
Authors

From the Departments of Pediatric Ophthalmology (JCE, DKC, EAP, ARB, KGY, PS) and Pediatrics, Section of Infectious Disease (HDJ, GJD-H, The Congenital CMV Longitudinal Study Group), Baylor College of Medicine, Houston, Texas; Texas Children's Hospital, Houston, Texas (HDJ, GJD-H, JM, JCE, DKC, EAP, ARB, KGY, JTK, PS, The Congenital CMV Longitudinal Group); and the Mitchel and Shannon Wong Eye Institute, Dell Medical School at the University of Texas–Austin, Austin, Texas (JCE).

Supported in part by the CMV Research Fund Donors at Baylor College of Medicine; the Woman's Hospital of Texas Research Foundation; the Office of Research Resources and the General Clinical Research Center for Children at Texas Children's Hospital and Baylor College of Medicine (NIH 5M0I RR00188-33); the Mental Retardation Research Center at Baylor College of Medicine (NIH-CHHD 5 P30 HD24064P); Research to Prevent Blindness, Inc., New York, NY; the Deafness Foundation, Houston, TX; the Vale Ashe Foundation, Houston, TX; the Maddie's Mission Foundation, Katy, TX; the Naymola Charitable Foundation, Beaumont, TX; the American Pediatric Society-Society for Pediatric Research Summer Student Research Program (NIHCHHD); and Merck & Co. and the Centers for Disease Control and Prevention (Cooperative Agreement FOA IP 10-006).

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

The authors thank The Congenital CMV Longitudinal Group (members listed in Table A, available in the online version of this article) and the study patients and their families for their lifetime of dedication and support for this study.

The Congenital CMV Longitudinal Study Group Members

Table A:

The Congenital CMV Longitudinal Study Group Members

Correspondence: Gail J. Demmler-Harrison, MD, Texas Children's Hospital, Feigin Center Suite 1150, 1102 Bates Street, Houston, TX 77030. E-mail: gdemmler@bcm.edu

Received: October 25, 2018
Accepted: February 14, 2019

10.3928/01913913-20190311-01

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