Hemoglobinopathies are due to the appearance of the pathological hemoglobin through structural modification of certain polypeptide chains of the normal hemoglobin (HbA). Sickle-cell disease is a frequent and severe hemoglobinopathy. About 230,000 children affected by sickle-cell disease are born every year in the sub-Saharan region, 2600 in North America and 1300 in Europe  . The molecular mechanism is the replacement of the glutamic acid by valine at the level of the codon 6 of the β globin gene, resulting in the production of the abnormal hemoglobin, hemoglobin S (HbS). Sickle cell disease is transmitted through the autosomal recessive mode: homozygote SS, heterozygote AS, double heterozygotes or “composite heterozygotes” SC (AS + AC), Sβ (AS + β heterozygote thalassemia).
AS heterozygotes are asymptomatic, SS homozygotes and double heterozygotes or “composite heterozygotes” SC, Sβ, SS + HPFH (hereditary persistence of fetal hemoglobin) are symptomatic and show the systemic manifestations of this disease. The ocular manifestations of sickle-cell disease are frequent and especially retinal with complications potentially associated with visual loss. Sickle cell retinopathy is frequently described in SS and SC homozygous forms and more rarely in AS   and Sβ  heterozygous forms. The study of Balo et al.  in Lomé showed that AS form was the most affected by retinopathy in 26.3%, followed by SS group in 11.05%.
The present study determines the frequency and severity of retinopathy among patients referred for ophthalmologic consultation by the Hematology Department, a reference unit for hemoglobinopathies care in Togo.
2. Material and Methods
This retrospective study over a period of three years (July 2013 thru June 2016) focused on the records of consecutive patients who are over 18 years old, sent to the Department of Ophthalmology for retinopathy by the Hematology Department. The diagnosis of sickle cell disease and genotypic accuracy were previously specified by the hematologist after hemoglobin electrophoresis: homozygote SS, heterozygote AS, double heterozygotes or “composite heterozygotes” SC (AS + AC), HPFH (hereditary persistence of fetal hemoglobin). All patients had a slit-lamp examination, the fundus by the Goldmann lens to assess the posterior pole and the entire retinal periphery. A distribution in the absence of sickle cell retinopathy, in non-proliferative sickle cell retinopathy (golden frosted, black sunburst) and in proliferative form according to Goldberg’s classification (Goldberg 1: peripheral arteriolar occlusions, Goldberg 2: peripheral arterio- venular anastomoses, Goldberg 3: preretinal peripheral neovascularization, Goldberg 4: intravitreal hemorrhage, Goldberg 5: retinal detachment)  had been made.
Patients with AS sickle-cell, an associated β-thalassemia or α-thalassemia were excluded from the study. The parameters analyzed in the study were age, sex, genotype (SS, SC, SF, and CC), and the severity of the retinopathy (non-proli- ferative and according to Goldberg).
The statistical analysis, χ2 was carried out through Epi info software version 7.0 with a significance p < 0.05. For qualitative variables, a 95% confidence interval (CI) was calculated.
Hundred and eighty-one patients among whom 105 women and 76 men (sex ratio = 0.72) were included in the study. The average age was 29.4 ± 9.84 years; [18 years; 70 years] Table 1.
Ninety-one patients were SS genotype (50.3%), sixty eight were SC (37.6%), twenty CC genotype and 2 were SF (1.1%) Figure 1.
Fifteen patients (8.3% CI [4.7 - 13.3]) showed a non-proliferative retinopathy (8 SS, 7 SC) and twenty-six patients (14.4% CI [9.6 - 20.3]) a proliferative sickle cell retinopathy.
Out of the twenty-six patients with the proliferative retinopathy, nineteen patients were SC genotype (20.9% of the SC), six patients were SS genotype (8.8% of the SS) and one patient of CC genotype (5% of the CC). 17.1% of female and 10.5% of male showed a PSR (Proliferative Sickle cell Retinopathy) Table 2. The average age of patients with a PSR form was 34 ± 8.5 years [18 years; 53 years].
These proliferative retinopathies were predominantly of stage 2 (34.6%), stage 3 (30.8%) and stage 4 (15.4%). The severe forms of proliferative retinopathy with a Goldberg’s stage ≥ 3 were found in 13 patients. Seventy-five percent of male (5 cases) with proliferative retinopathy had a severe form, and 38.9% (7 cases) of female had a severe form. Eleven of the severe forms were SC genotype (57.9%) and 2 were SS genotype (33.3%) Table 2.
Table 1. The socio-demographic characteristics of the patients: age (years) and sex (female, male).
Figure 1. Distribution of the different genotypes.
Table 2. Distribution of genotypes according to the severity of the retinopathy.
#Absence of retinopathy.
The absence of retinal angiography was a limit to our study.
In our study, we found a large proportion of the SS form (50.3%) followed by the SC form (37.6%) as reported in several studies   . The study of Diallo et al. had reported in its series a predominance of the SC form in 79.8% then the SS form 20.2%  . Fourteen point four percent (14.4%) had proliferative sickle cell retinopathy, which was low compared to that of Diallo et al.  with 20% and Tran et al.  with 59%. These differences may be due to the selection criteria because the majority of our patients were already followed in the Hematology Department. The study showed that SC form was the most represented in the proliferative forms 20.9% SC vs. 8.8% SS; as in the review 22% to 43% SC vs. 14% SS    . SC form was also the most represented in the severe proliferative forms (57.9% SC vs. 33.3%SS) like in the study of Leveziel et al.  54.4% SC vs. 18.1% SS. This confirms the findings that SC forms give retinal complications. In our study, male (75%) showed the severe forms more than female (38.9%). Male sex is a promoting factor for proliferation, as well as hemoglobin level higher than 12.5 g; blood hyperviscosity, hypoxemia, precarious medical treatment   .
Proliferative retinopathy was mainly found in SC genotype. More than half of proliferative sickle-cell retinopathies were severe with a male dominance. An early hematologic and ophthalmologic management and a regular follow-up will enable the reduction of blinding retinal complications.
Conflict of Interest
The authors declare no conflict of interest.
Approval for the study was obtained from the national medical ethic committee.