Prevalence and Characteristics of Cytomegalovirus Ocular Disease in Children: A Multi-Center Study

Figures & data

Table 1 Demographic Data

Sex (% of total population)		Total (n=793)
	Male	431 (54.3)
	Female	362 (45.6)
CMV viremia
	Age of CMV diagnosis (years)	5.9±0.2 (0–17.9)
	Length viremia (months)	15.9±2.2
	Maximum viral load (copies/mL)	103,645±24,715
Primary diagnosis (%)
	Solid organ transplantation	306 (38.6)
	Liver	137
	Renal	98
	Heart	49
	Lung	10
	Multiple solid organ transplants	9
	Small bowel	1
	Unspecified multi-organ	1
	Cancer	212 (26.7)
	Solid tumor	34
	Hematologic malignancy	178
	Primary immunologic	91 (11.5)
	Non-malignant blood disorder	52 (6.6)
	Congenital CMV infection	41 (5.2)
	CMV-related organ disease	13 (1.6)
	Other diagnoses	78 (9.8)
Treatment
	Steroid and steroid-sparing agent	273
	Steroid sparing-agent	223
	Steroid alone	63
	Neither steroid or steroid-sparing agent	232

Figure 1 Study methodology: (1) patient selection criteria; (2) data collection; and (3) breakdown of analysis.

Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia.

Table 2 Frequency of Clinical Findings and Odds Ratio of Death and Eye Exam by Multivariate Logistic Regression

Variable	OR of death (95% CI)	p-value
Cancer history	1.61 (0.99–2.63)	0.057
Transplant	0.44 (0.23–0.86)	0.016
Primary immunologic disorder	1.67 (0.64–4.42)	0.296
Max viral load	1.11 (1.0266–1.205)	0.009
SCT history	1.78 (1.075–2.969)	0.025
CMV treatment	1.05 (0.651–1.680)	0.851
Variable	OR of eye exam (95% CI)	P value
Cancer history	0.96 (0.65–1.44)	0.858
Transplant	0.24 (0.15–0.36)	<0.001
Primary immunologic disorder	1.41 (0.59–3.38)	0.435
Max viral load	1.25 (1.18–1.33)	<0.001
SCT history	1.07 (0.72–1.60)	0.739
CMV treatment	0.97 (0.67–1.42)	0.888

Abbreviations: CI, confidence interval; OR, odds ratio; SCT, stem cell transplant.

Table 3 Demographics of Patients with Confirmed CMV Ocular Disease

Gender	Total	Total group:
Male	10	431
Female	3	362
Primary diagnosis		(+) Ocular Symptoms
SCID status post-stem cell transplantation**	5*	0
Congenital CMV	3	1 (abnormal red reflex)
Hematologic malignancy (2 were status post-stem cell transplant**)	3	2 (decreased vision)
Evan syndrome status post-stem cell transplantation**	1	1 (red eye)
Medulloblastoma status post-bone marrow transplantation**	1	0
Eye findings
Retinitis	11
Optic nerve disease (atrophy)	1
Anterior uveitis	1
CMV viremia		Total group:
Age CMV viremia (SD), years	2.8±1.5	5.9±0.2
Average duration CMV viremia (SD), months	69.3±52.5	15.9±2.2
Maximim viral load (range), copies/mL	552,865 (150–4,208,000)	103,645±24,715
Concurrent immunomodulatory treatment
CMV IgG therapy	4
Steroid and steroid sparing agent alone	2
Steroid-sparing agent alone	1
Neither steroid or steroid-sparing agent	10
Mortality outcome		Total group:
Deceased	4/13 (31%)	113/793 (14%)
Average interval between last CMV PCR and time of death (months)	1.7±1.1	69.7±21.5

Notes: *SCID was statistically significant for the development of CMV ocular disease (p<0.001). **Stem cell transplantation was not statistically significant for development of CMV ocular disease (p=0.08) though 9/13 had transplantation.

Figure 2 Examples of fundus findings from our cases of pediatric CMV retinitis. (A) Color photo of left eye with hemorrhagic retinal necrosis (white arrow) and perivascular sheathing (yellow arrow) predominantly involving the macula in a 1-year old male with history of medulloblastoma and autologous hematopoietic progenitor cell transplantation. (B) Optos photo of left eye showing centripetal perivascular retinal whitening (white arrow) in a 15-year-old male with acute lymphocytic leukemia on maintenance chemotherapy of imatinib. (C) Color photos of right eye showing a central white granular lesion of the macula before (white arrow) and 2 months after (Orange arrow) systemic antiviral treatment in a patient with SCID. There was no peripheral involvement in either eye for this patient.

Figure 3 Risk factor-based screening recommendations.