|Year : 2017 | Volume
| Issue : 1 | Page : 20-25
Fundus changes in thalassemia in Egyptian patients
Ahmed Tamer Saif1, Passant Sayed Saif2, Ola Dabous3
1 Department of Ophthalmology, Fayoum University, Fayoum, Egypt
2 Department of Ophthalmology, Misr University for Science and Technology, October, Egypt
3 Medical Application Department, National Institute of Laser Enhanced Science, Giza, Egypt
|Date of Submission||22-Sep-2016|
|Date of Acceptance||14-Nov-2016|
|Date of Web Publication||6-Mar-2017|
Ahmed Tamer Saif
Department of Ophthalmology, Fayoum University, 5 Sherif St, Babel Louk Sq, Cairo 11111
Source of Support: None, Conflict of Interest: None
Aim The aim of this study was to evaluate the fundus changes in thalassemic patients in Giza and Fayoum Governorates.
Patients and methods Thirty thalassemic patients recruited from the Pediatric Hematology Clinic in Fayoum University Hospital, Misr University Hospital, and NILES Pediatric Clinic were included in the present study. All patients underwent complete ophthalmic examination and laboratory investigations.
Results The mean age was 10.7±5.9 (6–36) years. There were 20 male patients (66.7%), with a mean duration of disease of 7.1±7.1 years (3 months to 36 years). Patients were classified on the basis of hemoglobin (Hb) level into two groups: 7 g/dl or less (thalassemia major) and greater than 7 g/dl (thalassemia intermediate and thalassemia minor). There was a significant correlation between cup/disc (C/D) ratio and Hb level (P<0.05) and a nonsignificant correlation with color vision defect, retinal venous tortuosity, and arteriovenous (A–V) crossing changes. A highly significant correlation between serum ferritin and color vision defect (P=0.001), increased cup/disc ratio (P=0.001), venous tortuosity (P=0.001), and A–V crossing changes (P=0.002) was found.
Conclusion The majority of the ocular changes depend on the course and severity of thalassemia. Ocular complications can be prevented or delayed by reducing serum iron and ferritin levels with iron-chelating agents.
Keywords: C/D ratio, color vision defect, iron chelators, retinal venous tortuosity, thalassemia major
|How to cite this article:|
Saif AT, Saif PS, Dabous O. Fundus changes in thalassemia in Egyptian patients. Delta J Ophthalmol 2017;18:20-5
| Introduction|| |
Thalassemia major (TM) is a genetic disorder with a deficiency of red blood cells that manifests mainly during early infancy and requires blood transfusion for life. TM leads to reduced hemoglobin (Hb) production and hypochromic microcytic anemia associated with erythrocyte destruction and dysplasia. The course of the disease depends on adequate blood transfusion and other therapeutic facilities availability .
Adverse ocular changes include obliteration of iris pattern, lenticular degeneration, retinal pigment epithelial (RPE) degeneration and mottling, optic neuropathy, retinal venous (RV) tortuosity, and vitreoretinal hemorrhages that occur as a result of TM itself or as side effects of iron chelators .
Changes in the conjunctival and retinal vessels develop as early as the initial stages of thalassemia, presenting as twisting, dilatation, and irregular caliber of the veins, dilatation of the arteries, and reduction of their light reflex. Later, dystrophic and atrophic changes develop and thinning of its peripheral zone and deterioration of blood circulation in the central retinal zone occur . Decreased visual acuity (VA) in patients with TM is caused by the presence of retinal pathology .
Peripheral and/or macular pigmentary degeneration are the most common changes described. The earliest fundus changes reported are subtle opacification or loss in the transparency of the RPE and outer retina. These changes precede the development of RPE degeneration and mottling .
The aim of the present study was to evaluate the fundus changes in thalassemic patients in Giza and Fayoum Governorates.
| Patients and methods|| |
This study recruited 30 thalassemic patients from the Pediatric Hematology Clinic in Fayoum University Hospital, Misr University Hospital, and NILES Pediatric Clinic.
The study was approved by the institutional review board (IRB) and was conducted in accordance with the principles of the Declaration of Helsinki. A patient consent form was signed by the patients or their guardians.
- Thalassemia patients who tested positive for hemoglobin electrophoresis and dependent on blood transfusion.
- Patients 6 years of age or older.
- Patients on iron-chelating therapy and patients not on therapy.
- Presence of other hemoglobinopathies.
- Uncooperative patients.
- Anemia due to other causes.
- Congenital ocular anomalies.
- Previous ocular trauma.
- Autoimmune diseases such as Behcet’s disease or systemic lupus erythematosus.
- Any systemic disease such as diabetes or hypertension.
All patients were subjected to the following
- Full ocular and systemic history reporting.
- Laboratory investigations:
- Complete blood count (CBC) picture with blood indices using a Coulter Counter (Cell Dyne-1700; Abbott Diagnostics, Abbott Park, Illinois, USA).
- Serum ferritin evaluation using the enzyme-linked immunosorbent assay.
- Evaluation of fetal hemoglobin (Hb F) level using hemoglobin electrophoresis.
All patients underwent complete ocular examination: best-corrected visual acuity, color vision testing using the Nassar Color Test as it contains Arabic symbols that can be identified by the patients; anterior segment examination; and intraocular pressure evaluation. Fundus examination was performed by means of indirect ophthalmoscopy (Keeler, London, UK) with +20 D double aspheric macular lens (Volk Optical Inc., Mentor, Ohio, USA) and slit-lamp biomicroscopy with the +90 D biconvex lens (Volk Optical Inc.) to detect the presence of any fundus changes.
- Optical coherence tomography (OCT):
OCT was used to measure retinal nerve fiber layer thickness. It was performed using the OCT scanner (Cirrus HD-OCT Instruments; Carl Zeiss Meditec Inc., Dublin, California, USA).
Test results were documented for both eyes, but the result from the worse eye was used for statistical analysis.
- Collection of samples:
Under sterile conditions, 9 ml of venous blood was obtained by means of venipuncture and was divided as follows:
- A volume of 2 ml was collected in a sterile vacutainer containing EDTA as anticoagulant for CBC.
- A volume of 5 ml was collected in a sterile dry vacutainer. After the blood had clotted, the tube was centrifuged and serum was separated and divided into two equal volumes (in sterile Eppendorf tubes). One Eppendorf tube was used to assay liver and kidney functions and the other one was used to assay serum ferritin.
- A volume of 2 ml was collected in a sterile vacutainer containing EDTA as an anticoagulant for hemoglobin electrophoresis.
CBC was performed on an automated cell analyzer Sysmex KX − 21 (Sysmex Inc., Kobe, Japan) in hematology laboratory (normal total leukocytic count, 4000–12 000/cm; normal platelet count was 150 000–450 000/cm2).
Serum ferritin was evaluated on an automated chemistry analyzer (Advia Centaur; Siemens Healthcare GmbH, Erlangen, Germany). The assay was carried out using Advia Centaur kits (normal value: 22–322 ng/ml).Hemoglobin electrophoresis: Hemoglobin electrophoresis was performed using Sebia Hydragel 7 Hemoglobin (E) analyzer with Hyrys 2 Scanner (Sebia, Paris, France). The assay was performed using the CAPILLARYS Hb (E) kit (SEBIA - Parc Technologique Léonard de Vinci CP 8010 Lisses - 91008 Evry Cedex, FRANCE). The CAPILLARYS Hb (E) kit is designed for the detection of the normal Hb (A, F, and A2) and for the separation of the major Hb variants (especially S, C, E, or D) by means of electrophoresis in alkaline buffer (pH 9.4) with the CAPILLARYS system.
Different tests were analyzed in this study using SPSS Base 21.0 for Windows User’s Guide (SPSS Inc., Chicago, Illinois, USA).
- P-value=the probability/significance value.
- P>0.05, nonsignificant (NS);
- *P<0.05, significant at 0.05 level;
- **P<0.01, significant at 0.01 level.
| Results|| |
Thirty cases suffering from thalassemia syndrome were included in this study. The mean age of the patients was 10.7±5.9 (range=6–36) years, with 27 patients’ ages ranging from 6 to 15 years and three patients’ ages ranging from 15 to 36 years, as shown in [Table 1]. The mean duration of the disease was 7.1±7.1 years (range=0.4–36 years); the disease duration ranged from 3 months to 10 years in 24 patients and from 10 to 35 years in six patients, as shown in [Table 1].
|Table 1 Descriptive statistical analysis of all patients according to age and duration of disease|
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There were 20 male (66.7%) and 10 female patients (33.3%), as shown in [Table 2].
Thalassemia was divided into three types according to severity, Hb level, and frequency of blood transfusion (thalassemia major, intermediate, and minor). In the present study, patients were classified into two groups on the basis of Hb level of 7 g/dl or less (TM) and greater than 7 g/dl (thalassemia intermediate and thalassemia minor). Blood transfusions in β-TM aim to maintain the level of Hb at 1014 g/dl.
There was a significant correlation between cup/disc (C/D) ratio and Hb level (P<0.05) ([Table 3] and [Figure 1]) and a nonsignificant correlation between color vision defect, RV tortuosity, and A–V crossing changes.
|Table 3 Correlation between Hb, color vision defect, cup/disc ratio, retinal venous tortuosity, and A–V crossing|
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|Figure 1 Correlation between Hb, color vision defect, cup/disc (C/D) ratio, retinal venous (RV) tortuosity, and A–V crossing.|
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Twenty-eight patients (93.3%) received treatment regimens as blood transfusion, whereas two patients (6.7%) received supportive treatment without blood transfusion and four patients (13.3%) received blood transfusion with iron-chelating agents ([Table 4]).
|Table 4 Percentage distribution of all patients as regards the following parameters|
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Ocular manifestations were reported in nine patients with TM (30%), whereas 21 patients (70%) showed no ocular abnormalities.
Decreased VA was observed in 20 patients (66.7%) without fundus changes. The fundus changes inall 30 patients (60 eyes) were increased C/D ratio in nine eyes (15%), RV tortuosity in eight eyes (13.3%), arterial venous crossing changes in four eyes (6.7%) and color vision defects in four eyes (6.7%) as shown in [Table 5].
|Table 5 Percentage distribution of all patients as regards the following parameters|
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A highly significant correlation was reported between serum ferritin and color vision defects (P=0.001), increased C/D ratio (P=0.001), venous tortuosity (P=0.001), and A–V crossing changes (P=0.002), as shown in [Table 6].
|Table 6 Correlation between serum ferritin and different ocular manifestations|
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There was no significant correlation between frequency of blood transfusion and C/D ratio, color vision defects, A–V crossing changes, and RV tortuosity ([Table 7]).
|Table 7 Correlation between frequency of blood transfusion and different ocular manifestations|
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A highly significant correlation was reported between iron-chelating agents and fundus abnormalities detected as color vision defects, C/D ratio, RV tortuosity, and A–V crossing changes (P=0.001), as shown in [Table 8].
|Table 8 Correlation between iron-chelating agent, color vision defect, cup/disc ratio, retinal venous tortuosity, and A–V crossing|
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Night blindness, vitreoretinal hemorrhage, angioid streaks, RPE degeneration, mottling, or optic neuropathy were not detected in the current study.
| Discussion|| |
The patients with TM present with various ocular and systemic manifestations.
Ocular findings include decreased VA, color vision defects, night blindness, visual field defects, optic neuropathy, pigmentary retinopathy, RPE degeneration, increased cup/disc ratio, retinal vessel tortuosity, A–V crossing changes, vitreoretinal hemorrhage, chelating of metals in the retina, angioid streaks, and retinal microvascular abnormalities.
Iron-chelating agents such as desferrioxamine are associated with many ophthalmic changes.
We studied the various ocular manifestations of TM and the effect of iron-chelating agents on the eyes.
The results of the present study were based on data obtained from TM patients who belonged to the age group 6–36 years and are similar to the study by Incorvaia et al. . However, other studies in the western world have also been conducted in cases up to 45 years of age. The age disparity may be attributed to the lower survival rates among TM in our country, which may be due to poor compliance with therapy, unavailability of frequent blood transfusions, or the high cost of iron-chelating therapy.
The current study showed that TM is more prevalent in male population, with a male-to-female ratio of 2 : 1. However, Taneja et al.  reported a slight male predominance (1.25 : 1), whereas Gartaganis et al.  reported a male-to-female ratio of 1.07 : 1 and Gaba et al.  reported a ratio of 1.33 : 1.
In the present study, disease onset within the first year of the life was seen in 12 patients (40%), whereas two patients (6.7%) were diagnosed between 2 and 3 years of age and 15 patients (50%) were diagnosed after the age of 3. In the study by Taneja et al. , 36 patients (80%) were diagnosed with β-thalassemia within the first year of life, of whom 21 (58%) were diagnosed within 6 months of life, four patients (9%) between 1 and 2 years of age, two (4%) patients between 2 and 3 years, and three (7%) patients after 3 years of age.
The mean duration of disease in the current study was 7.1 years. The age at diagnosis is directly related to the time at which TM manifests itself. In the study by Taneja et al. , 80% of the patients were diagnosed within the first year of life, whereas in the study by Gaba et al.  55% of the patients were diagnosed during the first year of life. An earlier detection rate may be attributed to better and cheaper diagnostic facilities as well as mass media coverage, which helps in spreading awareness about the disease.
In the current study, ocular involvement was detected in 36.7% of the patients. This finding is similar to that reported in the study by Dewan et al. , who reported that 36% of patients had ocular manifestations, and the study by Gartagantis et al. , who reported that 41.3% had ocular involvement . However, Taneja et al.  reported ocular involvement in 58% of patients and Gaba et al.  reported ocular involvement in 71.4% of patients.
In the present study, we found a decrease in VA in 20 patients (66.7%). This is comparable to the findings of Taneja et al.  (67%), whereas contradictory to the findings of Gaba et al.  (37.1%) and Taher et al.  (19.4%). Children with TM are known to suffer from abnormal physical growth, and it may be associated with a high prevalence of refractive errors .
In the current study, two patients were diagnosed as having color vision abnormalities (6.7%), as in the study by Rahiminejad et al. , who reported that two patients had color vision defects.
In the current study, the frequency of blood transfusions was 93.3%. However, in the study by Taneja et al. , 25 patients (56%) received blood transfusions, with a mean of 176.15 (range=1–401).
In the current study, only four patients (13.3) received a blood transfusion with oral iron-chelating agent, whereas in the study by Taneja et al.  19 patients (45%) received subcutaneous desferrioxamine. The mean dose of desferrioxamine was 939.42 g (range=52–3744 g). Thirty-three patients (73%) received a mean dose of oral deferiprone of 2915.75 g (range=91.25–10 220 g).
In the current study, a significant correlation between blood transfusion and fundus changes in thalassemia was observed.
The authors found 20 patients (66.7%) with decreased VA (75% of patients receiving desferrioxamine), two patients (6.7%) with color vision abnormalities, six eyes (10%) with increased C/D ratio, three eyes (5%) with A–V crossing changes, and six eyes (10%) with RV tortuosity.
Seventeen patients (85%) who were not receiving iron-chelating agents had decreased VA, which is consistent with the findings of Taneja et al. . However, Taher et al.  reported that iron-chelating agents used had no influence on the decrease in VA. Lai et al.  did not report any acute visual toxicity linked to desferrioxamine intake or any child with color vision changes. Lam et al.  did not associate between the dose of desferrioxamine and ocular abnormalities.
In the present study, RV tortuosity was reported in eight eyes (13.3%). This incidence is higher than that reported in the study by Taneja et al.  (11%), Sorcinelli et al.  (5%), and Dewan et al.  (8%), whereas less than that reported in the study by Gaba et al.  (17.14%) and Taher et al.  (17.9%).
RV tortuosity was found in six of eight eyes receiving desferrioxamine therapy. Correlation of serum ferritin levels with RV tortuosity was statistically significant. These findings correlate with those of Abdel Malak et al. , who reported RV tortuosity in 40% of their patients receiving desferrioxamine therapy, and in 44.4% of the patients receiving deferriprone therapy, with no significant difference as regards the type of iron chelation with correlation of serum ferritin levels and serum iron levels with RV tortuosity. This is consistent with the findings of Taneja et al. , who reported more tortuosity in patients with higher serum ferritin levels. Similar observations were reported by Gaba et al. .
Increased C/D ratio was reported in nine eyes (15%) in patients with higher serum ferritin levels, whereas Taneja et al.  reported two patients (4%) with increased C/D ratio with a statistically significant correlation with serum ferritin levels. A large cup–disc ratio was also reported by Saif et al.  in patients with anemia.
In the current study, four eyes (6.7%) had arterial venous crossing changes and the authors did not find RPE degeneration or mottling. Chen et al.  did not report retinal pigmentary degeneration in patients receiving desferrioxamine, whereas Taher et al.  reported that patients on deferiprone were four times more likely to have RPE degenerations compared with patients on desferrioxamine.
Taneja et al.  reported that patients with RPE changes received larger doses of deferiprone and lesser doses of desferrioxamine, which may have had a role in RPE degeneration occurrence. The correlation of serum iron and ferritin levels with RPE degeneration or mottling were not statistically significant.
A large number of TM patients in the study had ocular involvement despite moderate doses of deferiprone and a high serum ferritin levels, which implicate the role of iron in ocular pathology.
Limitation of the present study is the inability to establish whether the ocular involvement was related to the disease or to the iron-chelating agents. This requires stoppage of chelating therapy. It should be kept in mind that both iron overload and iron-chelating agents may be mutually confounding factors in the causation of ocular changes in TM ([Figure 2]).
|Figure 2 Correlation between serum ferritin and different ocular manifestation.|
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| Conclusion|| |
Most of the ocular changes in TM were attributed to the course and severity of the disease. Reduction in serum iron and ferritin levels together with regular eye examination can aid in preventing or delaying ocular complications.
The Fayoum Ophthalmology Department council approved the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]