Ocular Signs Related to Overweight and Arterial Hypertension in Children: A Systematic Review

1. INTRODUCTION

Child obesity has been recognized as a global public health problem which can negatively affect almost all the body’s organs and cause relevant disorders such as asthma, early onset of puberty, glomerulopathy, misaligned lower limbs, hypertension, cardiovascular disease, white brain matter damage and mortality [1-6]. Worldwide, there are 1.1 billion obese and overweight people and 10%-25% of children are estimated to be affected by this situation [7-9]. Recent estimates calculate that there are between 42.4 and 51.8 million children and adolescents aged 0-18 in this context in Latin America [8].

With regard to children in particular, the mechanisms underlying the association between obesity and SAH and microvascular disease, however, have yet to be enlightened. Assessment of retinal circulation has been proposed as a way of estimating systemic microcirculation and detecting the first signs of systemic cardiovascular and cerebrovascular disease in clinical practice [10-12].

The morphology and flow in the retinal vessels (caliber, tortuosity, branching patterns, fractal dimensions, flow) are markers frequently analyzed. It is almost consensus that in adults the narrower the retinal arteriolar vessel, the greater the possibility of association with SAH [13], cerebrovascular accidents [11, 12, 14] and coronary artery disease [15, 16]; whilst the wider the retinal vein diameter, the greater the associations with systemic inflammation and obesity [17, 18]. Cross-sectional(CS) population-based studies have shown that increased body mass indices (BMI) are associated with retinal arteriolar narrowing and increased retinal venular diameter among adults [19-21]. These findings are in agreement with data from studies with healthy child populations, indicating a possible effect of obesity and/or SAH on early alterations to microvascular structure in childhood [22-25].

Despite the evidence, the results regarding independent association between obesity (with or without SAH) and alterations in retinal vessels caliber (RVC) in children and adolescents are heterogeneous and the mechanisms are still unclear [26]. The only review on this topic includes perinatal risk factors (low weight, gestational age), environmental factors (physical activity, diet, family hypertension), systemic factors (hypertension, obesity) and diseases associated with future cardiovascular changes. However, it limited searches to a few databases, restricted languages, included only articles accessible to the authors' library, and did not make a qualitative risk analysis of the studies [27].

Studies involving adult populations do not have full control over confounding factors inherent to this age group relating to arterial pressure, diabetes, smoking, use of medication and it is therefore of interest to know the results of studies conducted with healthy children and youth [22]. The body mass index (BMI) in children is considered normal between percentile 3 and 85; low weight below percentile 3; overweight between percentile 85 and 97 and obesity when above percentile 97, as established by the World Health Organization in 2007 for children and adolescents (10-19 years-old). These take into consideration adolescent growth spurt [26].

This study therefore seeks to assess, by means of a systematic review of observational studies, the presence of ophthalmological alterations in children and adolescents who are overweight or have SAH.

2. METHODS

2.3. Study Selection

The articles selected from the databases were divided into two batches under the responsibility of two reviewers each, so that there were four different reviewers overall. Article titles and abstracts were assessed independently by each reviewer. When abstracts did not provide sufficient information as to the eligibility criteria, the entire text was assessed. The reviewers assessed the full text of the articles independently from each other and determined study eligibility. Disagreements were solved by consensus and if they persisted the opinion of a fifth reviewer specialized in the theme in question was sought (Fig. 1).

3. RESULTS

Fig. (1) shows that 901 studies were identified, 19 of which were included in this analysis. Three studies assessed both SAH and overweight [34, 36, 37]. Further five studies assessed SAH [10, 38-41] and the remaining eleven studies assessed the effects of overweight [6, 22, 24, 25, 35, 42-47], as described in Tables (1 and 2). The methodological quality of the studies is described in (Table 3).

4. DISCUSSION

According to the findings of our systematic review, children with SAH and/or obesity may have retinal repercussions similar but not identical to those observed in adults, in particular arteriolar narrowing in hypertensive children and venular dilation in children with high BMI. This is due to several factors, including the status of the retinal vessels at the time of the onset of SAH, the duration, severity and response to its management as well as prevalent comorbidities (diabetes, hypercholesterolaemia) [10, 13, 18, 19].

This evidence comes from both direct measurement and also from analyses based on the principle of the fractal dimension, whereby rarefaction of the retinal vessels can be seen [38-42]. The following mechanisms have been proposed regarding venous dilation among the obese: increased blood volume and increased leptin levels (the latter stimulating nitric acid synthesis), and increased pre-inflammatory factors (TNFα) or inflammatory factors [38].

As such, these potential markers can be a basis for supporting diagnosis and control of these situations in childhood. Control of these factors could reduce the consequences for the target organs [48]. These vascular conditions leave traces of their presence from the onset and the marker can be used for following up on suspected cases. The difficulty lies in the routine inclusion of expensive retinal images and digital measuring systems for these vessels, considering that qualitative analysis restricts long-term follow-up of these findings to subjectivity. Moreover, as yet there is no standardized and universal acceptance or use of these quantitative estimation devices.

It must be taken into consideration that measurements made by computerized equipment are automatic estimates derived from non-uniform criteria or based on images subject to discrepancies. Moreover, the vascular zones analyzed are not always equivalent. In cases of axial myopia, or perinatal morbidities the retinal vessels tend to be narrower and these aspects may confound the results.

Based on the studies selected here, unanimity is lacking with regard to association between IOP and SAH and/or obesity [34, 35, 42, 44, 46]. Differing populations, different measurement methods (including body position), as well as the lack of more relevant data, such as corneal thickness, analysis of the optic disc and visual fields, prevent undeniable association from being established. The mechanisms suggested include (1) excessive intraorbital fat and blood hyperviscosity compromising venous drainage, (2) increased aqueous humour filtration owing to greater circulatory flow in the ciliary arteries, and (3) body position during tonometry, assuming that obese patients binding forward and often straining may cause alterations in measurements. It is appropriate to highlight that small differences in eye pressure measurements are not always clinically relevant [35].

The findings regarding refractive status and axial length were not different to those found in normal weight children [10, 34, 40, 42, 46]. Xiao and colleagues [26] found that microvascular alterations are only present in children over 12 years old, implying that obesity may be associated with microvasculature only in children near to puberty.

In adults and also similarly in children above 6 years old, the relationship between SAH and obesity, especially with regard to retinal vessels, has been demonstrated in a large number of publications. Arteriolar narrowing associated with SAH and venular dilation associated with obesity are markers of these situations. A recent systematic review and meta-analysis of 10229 adult cases concluded that in adults retinal arteriolar narrowing and retinal venular dilation are associated independently and significantly with higher risk of SAH, especially in people aged over 60. The study estimated that for every 1.12 mmHg increase in arterial pressure there was arteriolar reduction of 20μ. This data is relevant both for case prognosis and control [49].

According to the META-EYE Study Group [7] regarding a meta-analysis involving 44000 individuals, retinal arteriolar caliber reduces and venular caliber increases in obese adults when compared to those with normal weight, regardless of cardiovascular risk factors. In this case, an increase of 1 kg/m² is associated with a difference of 0.07μ [95%CI:-0.08-0.06] in arteriolar caliber and 0.22μ (95%CI:021-0.23] in venous caliber. Given that these amounts correspond to a less than 1% in relation to normal calibers, their clinical significance is not clear [7]. In children these proportions regarding artery calibers in SAH and vein calibers in cases with high BMI appear to be considerably similar [22]. Even in those aged under six years old it was demonstrated that BMI and systolic arterial pressure have inverse linear associations with retinal artery caliber, and BMI has a positive linear association with vein caliber. For every kg /m² increase in BMI, there was a 1.06 µm reduction in retinal artery caliber (p = 0.01) and 1.12 µm widening of vein caliber (p = 0.02). The findings were also similar in those whose BMI was ≥ 95%. And for every 10 mm Hg increase in systolic pressure a 1.70 µm reduction was found in retinal artery caliber (p = 0.02) [50]. So subtle differences are difficult to perceive in ophthalmoscopy, and depends on specific equipment.

The strength of this systematic review lies in the bringing together of specific studies with children, with no restriction as to language, to form a significant sample pool. There are many limitations: (1) different populations, non-standardized and diverse methods used to assess variables, resulting in possible overestimation or underestimation, (2) the absence of prospective studies, preventing an appreciation of the causal link and the evolution of the findings over time, (3) different or imprecise criteria principally in relation to defining obesity. It was also found that the use of BMI does not accurately reflect the form of adipose tissue distribution, nor does it distinguish fat deposition from muscle hypertrophy [38].

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