Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 30  |  Issue : 3  |  Page : 105-109

A Study of Ocular Side Effects of Blood Transfusions and Iron Chelators in Thalassemia Patients


1 Department of Ophthalmology, MGM Institute of Medical Sciences, Navi Mumbai, Maharashtra, India
2 Department of Paediatrics, MGM Institute of Medical Sciences, Navi Mumbai, Maharashtra, India

Date of Submission15-May-2021
Date of Decision10-May-2022
Date of Acceptance31-May-2022
Date of Web Publication26-Dec-2022

Correspondence Address:
Dr. Ayushi Choudhary
24, Mishra Vihar, Geeta Bhawan, Indore 452001, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njo.njo_32_21

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  Abstract 


Aim: To determine the ocular changes and importance of ophthalmic consults in thalassemia patients on iron chelating agents and regular blood transfusions. Settings and Design: A cross-sectional study was conducted among thalassemia patients who were on regular blood transfusion and iron chelators. Materials and Methods: A detailed history was obtained from 50 thalassemia patients included in the study including birth history, family history, and treatment history which was taken from the parents. Ophthalmic examination performed included visual acuity test for distant and near vision with Snellen chart, color vision obtained with Ishihara plates, contrast sensitivity performed with Pelli–Robson charts, Schirmer test conducted with Whatman strip, intraocular pressure obtained with Perkins tonometer, detailed anterior segment performed with Appasamy Slit Lamp biomicroscope and posterior segment examination with the aid of 90D lenses, and indirect ophthalmoscopy with 20D lenses performed after dilatation. Fundus photograph was taken for all the patients with ZEISS fundus camera. The findings were recorded and documented. Statistical Package AQ6 for the Social Sciences software was used to analyze data obtained. Results: Study group included 26 males (52%) and 24 females (48%) of varying age from 4 years up to 18 years of age. Presence of thalassemia disorder was noted in the family of 10 patients (20%). Five (10%) patients had mild visual impairment for distant vision. While, 18 patients (36%) had mild dry eye disease. Fundus abnormalities were seen in 14 patients as arteriovenous tortuosity, tessellated fundus, and desferrioxamine retinopathy. Decreased visual acuity, dry eye, and fundus abnormalities were seen in patients with serum ferritin levels >1000 ng/mL. Fundus abnormalities were seen in patients with higher serum ferritin levels (>1000 ng/mL) and longer duration of treatment. In total, ocular changes were seen in 31 patients (62%). Conclusion: Regular ophthalmic consult is necessary for all thalassemia patients on regular blood transfusion and chelation therapy to unmask ocular changes at an early stage and provide optimum visual care.

Keywords: AV tortuosity, blood transfusion, iron chelators, thalassemia


How to cite this article:
Ramakrishnan R, Choudhary A, Gandhi P, Agrawal M, Hastak A, Choudhary A. A Study of Ocular Side Effects of Blood Transfusions and Iron Chelators in Thalassemia Patients. Niger J Ophthalmol 2022;30:105-9

How to cite this URL:
Ramakrishnan R, Choudhary A, Gandhi P, Agrawal M, Hastak A, Choudhary A. A Study of Ocular Side Effects of Blood Transfusions and Iron Chelators in Thalassemia Patients. Niger J Ophthalmol [serial online] 2022 [cited 2023 Feb 6];30:105-9. Available from: http://www.nigerianjournalofophthalmology.com/text.asp?2022/30/3/105/365487




  Introduction Top


Thalassemia, a genetic disorder manifesting mainly during early infancy, occurs as a result of gene mutation encoding for beta chains of hemoglobin which leads to hypochromic microcytic anemia, excessive erythrocyte destruction, and dysplasia. Therefore, blood transfusion remains as the mainstay treatment to permit normal growth and development. Iron chelating agents are used as an adjunct to blood transfusion in the management of thalassemia patients to decrease iron reserve of the body as agglomeration of toxic amounts of iron causes organ failure. Adverse ocular changes occur due to thalassemia disorder itself or as side effects of iron chelators which include visual field defects, night blindness, lens opacities, obliteration of iris pattern, loss of color vision, dyschromatopsia, visual loss, lens opacities vitreoretinal hemorrhages, retinal venous (RV) tortuosity, retinal pigment epithelial (RPE) degeneration and mottling, optic disc edema, optic neuropathy, and optic atrophy.[1]

About 100,000 individuals are suffering from β-thalassemia syndrome in India. Every year about 300,000 to 400,000 babies are born with a severe hemoglobin disorder.[2]

Therefore, this study was conducted to identify the ocular changes in thalassemia patients on blood transfusion and iron chelators in order to make appropriate recommendations and promote the need of regular ophthalmic consult for early diagnosis and optimum visual care.


  Subject and Methods Top


A cross-sectional study was conducted among all thalassemia patients who were on regular blood transfusion and iron chelators after obtaining ethical approval from our institutional review board, informed consent from the parents, and assent from the children. Thalassemia patients who tested positive by hemoglobin electrophoresis and dependent on blood transfusion and iron chelating therapy aged between 4 and 18 years were included in this study. Patients who had congenital ocular defects, uncooperative to follow study instructions, or presence of any other blood disorder were excluded from this study. Thalassemia patients were examined in this study who presented to Paediatric Outpatient Department (OPD) over a period of 3 months. A detailed history including birth history, family history, investigative history (including serum ferritin levels, hemoglobin), and treatment history was taken from the parents. Systemic examination was done by the pediatrician. Ophthalmic examination performed included visual acuity test for distant and near vision with Snellen chart, color vision obtained with Ishihara plates, contrast sensitivity performed with Pelli–Robson charts, detailed anterior segment performed with Appasamy Slit lamp biomicroscope (Chennai, Tamil Nadu), Schirmer test conducted with Whatman strip (New Delhi, India), intraocular pressure obtained with Perkins tonometer (New Delhi, India), and posterior segment examination performed with the aid of 90D Volk lenses using Appasamy Slit Lamp biomicroscope and Appasamy Indirect Ophthalmoscope with 20D Volk lenses after dilatation. Fundus photograph was taken for all the patients with ZEISS fundus camera (Bangalore, India). The findings were recorded and documented. Statistical analysis was done using Statistical Package for Social Sciences (SPSS, MS Office Excel Sheet (v 2019, Microsoft Redmond Campus, Redmond, Washington, United States) version 26.0; IBM). For all the statistical tests, P < 0.05 was considered to be statistically significant, keeping α error at 5% and β error at 20%, thus giving a power to the study as 80%.


  Results Top


In this study, 50 individuals were examined. Study group included 26 males (52%) and 24 females (48%) [Figure 1] of varying age from 4 years up to 18 years of age who were diagnosed with thalassemia disorder and were undergoing treatment, that is, receiving blood transfusion and iron chelators. There were eight patients of age between 4 and 8 years, 27 between 9 and 13 years, and 15 between 14 and 18 years [Table 1] and [Table 2], [Figure 2].
Figure 1 Distribution of study population.

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Table 1 Descriptive statistics of study population

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Table 2 Distribution of study population as per age group

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Figure 2 Distribution of study population according to the age interval (in years).

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A detailed history revealed presence of thalassemia disorder in the family of 10 patients (20%) out of which two were pairs of twin sisters (8%), two (4%) inherited from their father, and four (8%) had siblings who carried the trait.

On visual acuity testing for distant vision with Snellen chart, five (10%) patients had 6/12 vision in both eyes, four (8%) patients had 6/9 vision in right eye, and three (6%) patients had 6/9 vision in left eye. Normal near vision (N6), normal color vision (17/17 plates), and normal contrast sensitivity (<2.178) was observed in all patients. Hence, a total number of five (10%) patients had mild visual impairment for distant vision.

Schirmer I and II test results ranged from 12 to 20 mm. Schirmer I test result of all patients was >15 mm. Schirmer II test result of 10 (20%) patients was 12 mm, of eight (16%) patients was 14 mm, and for the rest of patients was >16 mm. Hence, a total number of 18 patients (36%) had mild dry eye disease.

Anterior segment examination of all patients was normal. Posterior segment examination revealed fundus abnormalities in 14 (28%) patients. Ten (20%) patients showed arteriovenous tortuosity out of which six (12%) were males and four (8%) were females [Figure 3]. The tortuosity was seen in patients >7 years of age, with predominance at 13 years of age. Tessellated fundus was observed in three (6%) patients. Pattern dystrophy-like retinal pigment epithelium changes in the macula called as “desferrioxamine retinopathy” was seen in one patient aged 12 years [Figure 4]. These patients were on treatment of varying duration from 6 months to 4 years [Table 3]. While the rest did not show any fundus abnormality.
Figure 3 Fundus photograph showing arteriovenous tortuosity (AV).

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Figure 4 Fundus photograph showing desferrioxamine retinopathy.

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Table 3 Distribution of study population as per starting age of transfusion

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Ocular changes were studied with respect to serum ferritin levels. Decreased visual acuity was noted in patients with serum ferritin levels <500 ng/mL. Dry eye was seen in patients with serum ferritin levels between 500 and 1000 ng/mL. Decreased visual acuity, dry eye, and fundus abnormalities were seen in patients with serum ferritin levels >1000 ng/mL. There was no statistically significant correlation seen between ocular manifestations with respect to the number of blood transfusions.

Ocular changes were seen in seven patients undergoing treatment for thalassemia for <5 years, in 10 patients undergoing treatment since 5 to 10 years, and in 14 patients undergoing treatment for >10 years [Figure 5].
Figure 5 Number of patients showing ocular changes with respect to duration of treatment in years.

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  Discussion Top


Thalassemias are a category of disorders in which the ratio of alpha globin to beta globin production is disrupted. The production of the alpha or beta chains are decreased, resulting in either alpha-thalassemia or beta-thalassemia.[3] In alpha-thalassemia, the number of gene mutations inherited from parents depict the severity of this disorder, while in beta-thalassemia, it depends on the part of the hemoglobin molecule affected. Precursors of red blood cell in the bone marrow and circulation are destroyed causing ineffective erythropoiesis and hemolysis due to precipitation of unpaired chains. Therefore, affected individuals have varying degrees of anemia and extramedullary hematopoiesis resulting into iron overload, bone changes, and impaired growth.[4] In cases of severe thalassemia, complications like bone deformities, congestive heart failure, abnormal heart rhythms, developmental delay, etc. can occur.[5] Individuals with family history of thalassemia and certain ancestry like African, Americans, Mediterranean, and Southeast Asian descent are at a higher risk.[6] Iron overload is inexorable in thalassemia major patients as they receive constant blood transfusion. Accumulation of iron causes toxicity to many tissues resulting in heart failure, growth retardation, multiple endocrine abnormalities, cirrhosis, liver cancer, and retinopathy changes.[7]

Iron excretion is increased in urine and/or feces through chelating therapy to balance the rate of iron accumulation due to blood transfusion. Iron is required for essential physiological purposes. Therefore, a key challenge is to balance the benefits of chelation therapy with adverse effects of excessive chelation. To avoid excess chelation, careful dose adjustment and monitoring is necessary. Complications may be seen in young patients with low ferritin levels and high doses of chelating agents. Iron chelators are started at 2 years of age. Ocular toxicity usually presents as blurred vision, decreased visual acuity, night blindness, color vision impairment, cataract, foveomacular, paramacular, macular, papillary or peripapillary and peripheral degeneration, RPE opacification, RPE changes, optic disc edema, and optic atrophy.[1] Desferrioxamine retinopathy is seen in cases of desferrioxamine toxicity.[5] Regular serum ferritin level monitoring and maintaining the desferrioxamine dosage with therapeutic index [daily dose per body weight (mg/kg) divided by serum ferritin level (mg/L)] below 0.025, may provide safety against the development of rapidly progressive severe irreversible retinopathy.[8]

Abdel-Malak et al.[9] conducted a study and observed RV tortuosity in 40% of their patients receiving desferrioxamine therapy and in 44.4% of the patients receiving deferiprone therapy, with no significant difference in relation to the type of iron chelation with correlation of serum ferritin levels and serum iron levels. Taneja et al.[10] conducted a study and observed tortuosity in patients with higher serum ferritin levels. They also observed that patients with RPE changes received larger doses of deferiprone and lesser doses of desferrioxamine, which may be suggestive to have a contributory role in RPE degeneration. Taher et al.[11] observed in their study that patients on deferiprone were four times more likely to have RPE degenerations as compared with patients on desferrioxamine.

Similar to above studies, we noted fundus abnormalities in patients with higher serum ferritin levels (>1000 ng/mL) and longer duration of treatment in our study population.

In our study, various ocular changes were seen in 31 thalassemia patients (62%) receiving blood transfusion and desferrioxamine. Primary outcome measure was the ocular manifestation seen in the form of fundus abnormalities. Secondary outcome measures were to assess visual acuity impairment and correlation with serum ferritin levels. However, it is difficult to ascertain whether the disorder itself or blood transfusion and chelation therapy is responsible for ocular pathology. There was no correlation found between the number of blood transfusions and ocular manifestations. All patients in this study were on desferrioxamine, therefore it was not possible to compare various iron chelators and their ocular effects.

Patients should undergo baseline examination prior to therapy to ascertain normal visual function and detect pretreatment disorders which otherwise may be missed. Ocular changes are reported with desferrioxamine and deferiprone and the disease itself is also attributed to cause many ocular changes, which is difficult to distinguish. The mainstay of current treatment is to use iron chelating agents as an adjunct in order to reduce serum iron and ferritin levels. Regular dose monitoring and ophthalmic examination helps to prevent or control ocular side effects and complications.

Therefore, regular ophthalmologic consult is necessary for all thalassemia patients on regular blood transfusion and chelation therapy to unmask ocular changes at an early stage and provide optimum visual care.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Liaska A, Petrou P, Georgakopoulos CD et al. β-Thalassemia and ocular implications: a systematic review. BMC Ophthalmol 2016;16:102. doi: 10.1186/s12886-016-0285-2.  Back to cited text no. 1
    
2.
Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med 2012;2:a011692. doi: 10.1101/cshperspect.a011692.  Back to cited text no. 2
    
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Brancaleoni V, Di Pierro E, Motta I, Cappellini MD. Laboratory diagnosis of thalassemia. Int J Lab Hematol 2016;38(Suppl 1):32–40. https://doi.org/10.1111/ijlh.12527.  Back to cited text no. 3
    
4.
Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol 2009;16:187–94. doi: 10.1097/MOH.0b013e32832990a4.  Back to cited text no. 4
    
5.
Gorezis S, Asproudis I, Chalasios N et al. Contrast sensitivity in patients with beta-thalassemia major and sickle cell disease under regular transfusions and treatment with desferrioxamine. Open Ophthalmol J 2010;4:39–41. doi: 10.2174/1874364101004010039.  Back to cited text no. 5
    
6.
Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med 2013;3:a011775. doi: 10.1101/cshperspect.a011775.  Back to cited text no. 6
    
7.
Taher AT, Saliba AN. Iron overload in thalassemia: different organs at different rates. Hematology Am Soc Hematol Educ Program 2017;2017:265–71. doi: 10.1182/asheducation-2017.1.265.  Back to cited text no. 7
    
8.
Di Nicola M, Barteselli G, Dell’Arti L, Ratiglia R, Viola F. Functional and structural abnormalities in deferoxamine retinopathy: a review of the literature. Biomed Res Int 2015;2015:249617. doi: 10.1155/2015/249617.  Back to cited text no. 8
    
9.
Abdel-Malak DS, Dabbous OA, Saif MY, Saif AT. Ocular manifestations in children with β thalassemia major and visual toxicity of iron chelating agents. J Am Sci 2012;8:633–8.  Back to cited text no. 9
    
10.
Taneja R, Malik P, Sharma M, Agarwal MC. Multiple transfused thalassemia major: ocular manifestations in a hospital-based population. Indian J Ophthalmol 2010;58:125–30. doi: 10.4103/0301-4738.60083.  Back to cited text no. 10
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11.
Taher A, Bashshur Z, Shamseddeen WA et al. Ocular findings among thalassemia patients. Am J Ophthalmol 2006;142:704–5. doi: 10.1016/j.ajo.2006.04.030.  Back to cited text no. 11
    


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