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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 88-93

Ocular manifestations in children and adolescents with sickle cell disease attending a Pediatric Hematology Unit in Damanhur Teaching Hospital


1 Department of Pediatric, Damanhur Teaching Hospital, Alexandria, Egypt
2 Department of Ophthalmology, Damanhur Teaching Hospital, Alexandria, Egypt
3 Department of Clinical Pathology, Damanhur Teaching Hospital, Alexandria, Egypt

Date of Submission30-Mar-2020
Date of Acceptance21-Apr-2020
Date of Web Publication5-Oct-2020

Correspondence Address:
MD Saad S Abo-Zied
Department of Pediatric, Damanhur Teaching Hospital, Alexandria, Egypt. 33743 Sidi Salm Post Office
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_23_20

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  Abstract 


Background Sickle cell disease (SCD) is the most common genetic disease worldwide. It is usually accompanied with painful crisis. Microvascular occlusions are common and affect different systems, among which is the ocular manifestations.
Aim This study aimed to assess retinal changes in patients with SCD and its correlation with hematological parameters and if there is a link between a pretransfusion hemoglobin level and ocular manifestations or not.
Patients and methods This study was conducted in the Pediatric Hematology Unit of Damanhur Teaching Hospital including patients coming regularly to sickle cell OPD for follow-up, those who were admitted for sickle cell crisis in internal medicine ward, as well as obstetrics/gynecology patients who were found to be sickle cell positive (SS pattern). In this cross-sectional study, 30 steady-state patients (60 eyes) aged 2–26 years (22 children and eight young adults) with an established diagnosis of SCD (16 with homozygous SS and 14 with S/b thalassemia) underwent complete ophthalmic examination with dilated fundoscopy. Hematologic investigations and ophthalmic investigations (visual acuity, slit-lamp biomicroscopy, and fundoscopy) were done and compared. For statistical analysis, SPSS software was used.
Results The study showed that 70% of the patients with SCD with hemoglobin less than or equal to 7 g or less had ocular abnormalities in the form of nonproliferative retinopathy, proliferative retinopathy, and refractive errors.
Recommendations Based on these observations, we recommend that all children with SCD (SS, S/B) should have regular ophthalmic examination including fundoscopic examination to screen for sickle cell retinopathy beginning at the age of 12 years.

Keywords: Hbss pattern, hemoglopinoptheis, ocular manifestations, sickle cell disease, sickle cell retinopathy


How to cite this article:
Abo-Zied SS, Elgemaey HEM, Abd-Aal HM. Ocular manifestations in children and adolescents with sickle cell disease attending a Pediatric Hematology Unit in Damanhur Teaching Hospital. Alex J Pediatr 2020;33:88-93

How to cite this URL:
Abo-Zied SS, Elgemaey HEM, Abd-Aal HM. Ocular manifestations in children and adolescents with sickle cell disease attending a Pediatric Hematology Unit in Damanhur Teaching Hospital. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 20];33:88-93. Available from: http://www.ajp.eg.net/text.asp?2020/33/2/88/297244




  Introduction Top


Sickle cell disease (SCD) is the most common genetic disease worldwide. In Egypt, hemoglobin (HbS) carrier rates vary from 9 to 22% with a heterogeneous distribution [1]. Among Egyptians, most of the reported globin gene haplotypes are the African ones, and the SCD phenotype is severe [2].

SCD is a chronic hemolytic anemia characterized by the occlusion of small blood vessels, tissue ischemia, and effects on various organs, including the eyes and brain [3].

SCD is transmitted through an autosomal recessive pattern of inheritance. The disease is expressed when two copies of HbS combine (HbSS). HbC is caused by a glutamic acid-to-lysine change in the β-globin molecule. Compound heterozygous disease results when one copy of HbS and another β-globin variant, such as HbC, combine. Individuals with one copy of the HbA molecule and one copy of the HbS molecule carry sickle cell trait [4]. Despite being characterized by the same point mutation, the clinical course of SCD is extremely variable, ranging from mild to very severe depending on the different genotypes [5],[6].

Painful crisis and severe hemolytic anemia are the two most common systemic complications [7]. However, ocular manifestations are usually mild and asymptomatic [8]. Ocular changes such as conjunctival sickling sign at the conjunctiva [9] and iris atrophy have been noticed [10]. Changes over the other vascular regions of the eye are seen in the choroid, optic disc, and the retina [11]. Although nearly all structures in the eye are affected in SCD, the vision-threatening problems are owing to retinal neovascularization [11],[12]. Sickle cell retinopathy develops in up to 42% of individuals during the second decade of life. A complication of proliferative sickle cell retinopathy (PSCR) is a major contributor to vision loss and visual impairment in 10–20% of affected eyes [13],[14].

Microvascular occlusions being the most common cause of complications and patients who experience repeated episodes of vaso-occlusion are vulnerable to visual loss, causing blindness [15],[16].


  Aim Top


This study aimed to assess retinal changes in patients with SCD and its correlation with hematological parameters and if there is a link between a pretransfusion Hb level and ocular manifestations or not.


  Patients and methods Top


This was a cross-sectional study conducted at the Pediatric Hematology Unit, Damanhur Teaching Hospital, on attending patients having SCD, between March 2019 and September 2019. A total of 30 patients (60 eyes) aged 3–26 years (22 children and eight young adults) with an established diagnosis of SCD [23 with homozygous SCD (SS) and seven with sickle-beta thalassemia (S/b)] were enrolled in the study. Patients were allowed to participate in the study only after required consents were willingly given by the patients and/or their guardians. Patients comprised 17 females and 13 males. All recruited patients were in a steady-state attending for a routine follow-up visit.

The study protocol was approved by the Ethical Committee of Damanhur Teaching Hospital, Egypt, according to the Institutional Committee for the Protection of Human Subjects.

Study population

All cases of SCD were diagnosed by Hb electrophoresis (23 with homozygous SS and seven with S/b thalassemia) in Damanhur Teaching Hospital and were examined for ocular manifestations (conjunctival sickling sign at the conjunctiva, refractive errors, and iris atrophy and changes over the vascular regions of the eye seen in the choroid, optic disc, and the retina).

Sample size

A total of 30 cases were included.

Inclusion criteria

Patients with SCD who came for regular follow-up or admitted for sickle cell crisis were included.

Exclusion criteria

The following were the exclusion criteria:
  1. Patients with psychiatric disease, previous ocular trauma, diabetes mellitus, hypertension, or decreased visual acuity (6/60).
  2. Retinopathy owing to any cause other than SCD.
  3. Anemias other than SCD.
  4. Patients with sickle cell trait and other genetic hemoglobinopathies other than SCD.


Procedures

All patients confirmed to have sickle cell anemia by Hb electrophoresis were included in this study, and the following investigations were done for every case ([Table 1]):
  1. Complete blood count, serum bilirubin, reticulocyte, and lactate dehydrogenase levels. Blood sampling was withdrawn before transfusion to correlate between pretransfusion Hb and abnormal eye findings.
  2. Detailed ocular examination was done as follows:
    1. Assessment of visual acuity using Snellen’s chart.
    2. Anterior segment structures, conjunctiva, cornea, iris, and lens were examined using the slit-lamp examination.
    3. Indirect ophthalmoscopy was carried out for lesions in the posterior segment. 20 D lens was used to examine the peripheral retina.
    4. Fundus examination with a binocular indirect ophthalmoscope and slit-lamp biomicroscopy. Herein, 78 and 90 D lenses were used in silt-lamp biomicroscopy to examine optic disc changes and macular changes.
Table 1 Goldberg classification followed for classifying sickle cell retinopathy if present [17]

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Statistical analysis

SPSS software was used for statistical analysis, and the collected data and results obtained were interpreted in the form of tables. Analyses were conducted using SPSS (v. 20, IBM SPSS Statistics, Chicago, IL, USA).


  Results Top


Visual acuity was 6/6 bilaterally in 28 patients; however, two patients with SS had an impaired visual acuity of 6/36 and 6/18, respectively, owing to errors of refraction. None of our patients had any visual symptoms. Normal intraocular pressure was observed in all patients.

[Table 2] demonstrates the clinical characteristics of patients with and without retinal lesions. Patients showing retinal lesions were significantly older and had a longer disease duration. Females are more affected than males. Comparing frequencies of disease-related events (acute chest syndrome, pulmonary hypertension, bone disease, and leg ulcers), vaso-occlusive events, hospitalization, and transfusion frequencies showed no significant differences between patients with and without nonproliferative retinopathy (NPR). Splenectomy showed significantly higher frequency in patients with nonproliferative retinopathy P=0.004).
Table 2 Clinical characteristics of patients according to retinal lesions

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As shown in [Table 3], comparison of hematological indices of patients without and with NPR revealed significant differences between both groups regarding Hb, red blood cell, red cell distribution width, mean corpuscular volume, and mean platelet levels. Patients with NPR had a higher mean of mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration levels; however, the difference was insignificant.
Table 3 Comparison of hematological parameters in positive and negative patients for ocular abnormalities

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[Table 4] describes the correlation between Hb level and other complete blood count parameters. There was a significant positive correlation between Hb level and total red blood cells, total white blood cells, and platelet count. On the contrary, there was a significant negative correlation between Hb level and red cell distribution width and mean corpuscular volume. Regarding the relation between Hb level and mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, the correlation was nonsignificant.
Table 4 Correlation of hemoglobin % with other hematological parameters (Pearson’s correlation coefficient)

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[Table 5] shows the distribution of ocular changes in SCD cases according to Hb level. The ocular changes were present in the cases with Hb level less than 7 g/dl, whereas other cases with Hb levels above 7 g/dl did not show retinal lesions.
Table 5 Ocular changes according to the hemoglobin level in sickle cell disease cases

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[Table 6] demonstrates that normal fundus was present in 25 (83.3%) patients (13 SS and 12 S/b). The overall frequency of retinal lesions was 16.6% (10 and 6.6% of patients with SS and those with S/b, respectively). Proliferative retinopathy was absent, and NPR was evident in five cases of all enrolled patients.
Table 6 Retinal manifestations among the studied sickle cell disease cases

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  Discussion Top


Patients with SCD are known to manifest different types of ocular problems, such as NPR, proliferative retinopathy, and refractive errors [18]. Irrespective of any ocular complaints, a search was made for ocular changes among the 30 SCD-positive patients. Of the 30 SCD-positive patients, 22 (73%) cases were below 20 years of age, with the youngest patient being 3 years old. A total of 17 (56.6%) patients were female and 13 (43.4%) were males. Females were more affected than males. Such sex predilection had been observed in other studies [19],[20]. However, other cohorts did not show any sex predominance for retinal changes or proliferative retinopathy, and this may be attributed to the smaller sample size, as they explained [21]. Changes in visual acuity among our patients were attributed to refractive errors. None of the previously reported causes of visual impairment in patients with SCD such as optic atrophy or central retinal occlusion were observed in the current study.

Fundus examination in the 30 patients revealed the absence of proliferative sickle retinopathy in concordance with many other studies, which reported that proliferative retinopathy in children with SCD was not detected [18],[21],[22],[23].

Excluding refractive errors, the overall frequency of ocular lesions in the study was five (16.6%) cases who had nonproliferative sickle retinopathy, corroborating with previous studies which found that sickle retinopathy develops in the range of 16.7–96.3% for nonproliferative sickle retinopathy and 0–11.1% for proliferative sickle retinopathy [21],[24],[25].

It should be noted that 83.3% of the patients with SCD with Hb less than 7 g% had some ocular changes. Pallor, icterus, and vascular changes (90.47%) were observed in the conjunctiva. The vascular changes were of grade I in the form of comma shaped or corkscrew shaped or abnormally long linear dilatations of vessels still connected to the vascular network with the sludged flow. They were mostly observed in the bulbar conjunctiva covered by eyelids. Such changes in various degrees have been observed in SCD and sickle cell HbC disease (97.4%) other than sickle cell trait [19],[22],[25].

The present work found significant changes in the major retinal vessels (28.57%). The major retinal vessels were dilated, full, and tortuous, with the veins being more tortuous than arteries. In some cases, the arteries were pale and narrow. The peripheral vessels were tortuous and sometimes occluded, but in a few cases, the arterioles were chalky white in color, associated with perivascular sheathing, occlusion, and tortuosity. Similar findings have been documented by other authors. They found peripheral vessel disease in 93.4% and major retinal vessel changes in 10.5% of HbSS cases [19], whereas others found venous fullness and venous tortuosity in 18 and 24% of their series [20]. Hemorrhage (57.14%) and neovascularization (14.28%) were also observed in the peripheral retina [24]. Retinal hemorrhage (3.2 and 2.6%) and tortuosity and dilatations of capillary network with microaneurysmal formation and neovascularization (36.4 and 39.5%) in the HbSS cases had been found in other two studies [19],[26]. Other investigators did not report any case of retinal hemorrhage in their series (instead they observed vitreous hemorrhage in one case) [20],[26].

The majority of cases with ocular involvement in all categories of hemoglobinopathies were within the third decades of life [27], and also we found that the highest prevalence was in the third decade as observed in this study. PSCR is rare in the first decade, indicating that repeated retinal damage occurs likely over time [28].

Incidence of PSCR increased with increasing age, and spontaneous regression occurred in 32% of PSCR eyes [29]. Three studies had observed the mean age for ocular changes was 22–28 years [16],[29],[30], whereas other studies had seen observed maximum changes in 10–20 years [21]. This study was in Jamaica in elderly age groups and showed that the incidence of peripheral vascular disease appears to increase with age. Another study found that most cases with ocular changes range between 20 and 30 years [31].

Most cases of different hemoglobinopathies had ocular changes in moderate and severe degrees of anemia (<7 g/dl of Hb). However, the comparison of the prevalence of ocular changes in different Hb concentrations and in various hemoglobinopathies of this study indicates that besides anemia, the abnormal sickle Hb is the prime cause for the ocular changes (e.g. in 7–10 g/dl of Hb range, indicating that simple anemia is not the only cause), corresponding with other studies [32].


  Conclusion Top


A visual loss that occurs owing to vaso-occlusive crises can be prevented in patients of SCD through early ocular diagnosis, as it would seem logical to assume that patients with SCD experience repeated episodes of vaso-occlusion might be most vulnerable to ocular pathology. Although NPR was found in this study, PSCR was not detected in the pediatric age group. Therefore, this study attempts to recommend including ocular examination in routine investigations of sickle cell tests and routine follow-up checkups in diagnosed cases of SCD, thus protecting them from visual impairment and visual loss.

Acknowledgements

The research was supported by Alexandria Faculty of Medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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