Corneal and lens densitometry evaluation with Pentacam HR in children and adolescents with beta thalassemia major: a case–control study

In the current study, we aimed to measure the corneal and lens density in β-thalassemia major patients using the non-invasive Pentacam to early detect disease and therapy related ocular complications prior to development of clinically evident symptoms. There are several studies reporting the ocular complications of patients with β-thalassemia major receiving iron chelating therapy [15,16,17,18,19]; however, very limited studies investigated early ocular complications in β-thalassemia major patients using Scheimpflug imaging [20].

In the current study, we observed that patients with β-thalassemia major had a significantly lower corneal densitometry measurements at anterior 0–2, 2–6, 6–10 mm zone, all central layer zones, posterior layer at 0–2, 2–6, 6–10, and right 10–12 mm zones, and total layer at 0–2, 2–6, 6–10 mm zones when compared to controls. ECD was found to be significantly lower among patients group in specular microscopic evaluation.

In consistence with our finding, Ulutaş and Kazancı included 32 patients with thalassemia in a study and detected lower density only in the posterior 60-micron corneal layer, and ECD value was lower in thalassemia group; however, the difference was not statistically significant [20].

The hypoxia that stems from the chronic anemia in β-thalassemia patients contributes to changes in many organs especially those with indirect vascularity as cornea and lens which depend on vitreous and aqueous diffusion. Consequently, those organs become more liable to ischemic alterations. The clarity of the cornea is critical for the precise corneal function and is maintained by increased metabolic activity of endothelial cells with higher oxygen requirements; therefore, the ischemia affecting the corneal clarity may be a start for corneal opacification [21]. In the current study, the endothelial cell density, which constitutes a part of the luminescent corneal tissue, is decreased. Therefore, the decrease in the corneal densitometric values might develop as a result of the alterations in the structure of corneal endothelium and the cell loss [20, 22].

In our study, K1, K2, and CV were detected to be significantly lower in cases in relative to controls. Previous studies have investigated the biometric measures and errors of refraction in patients with β-thalassemia and reported that ACD is shorter, cornea becomes steeper, and lens is thicker than controls. It was postulated that these changes are compensatory for growth restriction resulting from the deficiency in growth hormone as well as the skeletal orbital changes that occur in β-thalassemia patients [5, 23, 24].

Regarding the lens densitometry parameters, we could not detect a significant difference between β-thalassemia major cases and controls in terms of lens thickness; however, a statistically significant increase in the lens densitometry measurement values in thalassemic group was detected in all the three zones (P < 0.001). Moreover, a positive correlation between left PDZ1% and deferasirox dose was found (r = 0.307, P = 0.036), and left lens thickness increased with more frequent transfusion (r = − 0.338, P = 0.02). These findings propose that lens clarity becomes impaired in β-thalassemia cases.

Lens is also avascular section which requires higher oxygen levels for precise vision. Previous researches reported an increased lens thickness in thalassemic cases [23,24,25]. It is worth mentioning that the reported prevalence of cataracts in β-thalassemia patients reached 6.3% up to 45.7% [4]. The exact mechanism behind lens affection in β-thalassemia patients has not been fully compiled yet [20]. The longstanding hypoxia caused by the chronic anemia distorts the structure of the lens and cataract might occur. It is argued that multifactors contribute to the progress to cataract in those patients such as the oxidative damage of the lens by iron accumulation or disruption of oxidant/antioxidant balance, nutritional deficiencies, and the use of iron chelators [26, 27]. Significant correlations of lens opacity with increased level of ferritin and frequency of transfused blood were detected by Taneja et al. [4], also reported a higher prevalence of cataract with desferrioxamine therapy when compared to deferiprone therapy. The relationship between lens opacity and different iron chelators was reported such as deferoxamine [25, 27] and deferiprone [28]; however, other studies could not document this significant relationship [18, 23].

On the other hand, Ulutaş and Kazancı [20] found that lens densitometry in all zones revealed similar findings in both thalassemics and controls and reported that the maximum lens density was increased in thalassemia patients; however, no statistically significant difference was detected.

Indeed, numerous factors may lead to that discrepancy among different studies such as different samples size, some studies excluded patients with cataract and others did not, different methodology with use of Pentacam not ultrasonic evaluation. Also, the studies included patients who received different iron chelation therapies, in addition to the difference in other confounding risks that could influence ocular health outcomes in beta-thalassemia patients.

Further longitudinal studies are still needed to establish a correlation between lens parameters and iron chelators, evaluating the impact of different iron chelators and different doses on development of lens thickness and opacities.

It worth mentioning that despite we have only included subjects with normal range of blood glucose level, we found significant higher levels among cases when compared to controls which highlights the importance of early screening and close monitoring of blood glucose parameters in those patients; however, no correlation with any of the corneal and lens densitometry measurements was detected in our study. Further research is required to provide a practical guide for early detection of glucose dysregulation in β-thalassemia major cases and to detect the relation with early ocular complications in such patients.

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