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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 26  |  Issue : 4  |  Page : 205-210

Ocular manifestations of leukaemia: A teaching hospital experience


1 Department of Ophthalmology, Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria
3 Department of Radiation Oncology, Lagos University Teaching Hospital, Lagos, Nigeria

Date of Web Publication4-Oct-2019

Correspondence Address:
Dr. Olubanke Theodora Ilo
Department of Ophthalmology, Lagos University Teaching Hospital, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_50_19

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  Abstract 


Background: Knowledge of the ophthalmic manifestations of leukaemia is important not only because of the frequency with which changes are seen but because the eye often reflects the disease state of the illness, and once identified, prompt referral, early treatment can be instigated, blindness can be averted and a life may be saved. These manifestations are often overlooked because of the underestimation of the magnitude of the ocular sequelae which may be blinding. Aim: This study aims to describe the ophthalmic findings in adult leukaemic patients at two teaching hospitals in Lagos, Nigeria. Patients and Methods: This was a clinic-based, comparison multicentre study conducted at Lagos University Teaching Hospital and Lagos State University Teaching Hospital over a 9-month period of May 2012–January 2013. The cases were newly diagnosed leukaemic patients (acute and chronic) from the haematology clinics. Controls were escorts of apparently normal patients. Detailed ocular examination was carried out after written informed consent was obtained. Analysis was done using SPSS 17. Results: A total of 160 eyes in 80 individuals examined comprised forty cases and forty controls. The results of the cases were compared with the age- and sex-matched controls. Leukaemic-related ophthalmic manifestations were present in 56 eyes (70.0%) of the cases studied. Findings in cases were periorbital oedema in 8 eyes (10%), subconjunctival haemorrhage in four eyes (5%), intraretinal haemorrhage as found in 25 eyes (31.3%), retinal venous tortuosity in 21 eyes (26.3%), Roth spots in 19 eyes (23.8%) and retinal infiltrates in 17 eyes (21.3%). Conclusion: Ophthalmic disorders occur in adult patients living with leukaemia. Prompt initial and periodic ophthalmic evaluation is recommended in all leukaemic patients.

Keywords: Adult patients, blindness, leukaemia, ophthalmic manifestations


How to cite this article:
Ilo OT, Adenekan AO, Alabi AS, Onakoya AO, Aribaba OT, Kehinde MO, Salako O. Ocular manifestations of leukaemia: A teaching hospital experience. Niger Postgrad Med J 2019;26:205-10

How to cite this URL:
Ilo OT, Adenekan AO, Alabi AS, Onakoya AO, Aribaba OT, Kehinde MO, Salako O. Ocular manifestations of leukaemia: A teaching hospital experience. Niger Postgrad Med J [serial online] 2019 [cited 2019 Oct 16];26:205-10. Available from: http://www.npmj.org/text.asp?2019/26/4/205/268594




  Introduction Top


Leukaemia is a white blood cell disorder that may have ophthalmic manifestations which may be ocular, orbital, adnexal or neuro-ophthalmic.[1] It is a common cause of neoplastic disease and the 11th most common cause of cancer-related death.[2] Global statistics since 2000 shows that over 200,000 adults and children die from leukaemia yearly. This represents about 3% of the almost 7 million deaths due to cancer yearly and about 0.35% of all deaths from any cause. 90% of all leukaemias are diagnosed in adults, with acute myeloblastic leukaemia (AML) and chronic lymphocytic leukaemia (CLL) being most common in adults. It occurs more commonly in the developed country.[2]

Traditionally, leukaemias have been described as acute or chronic, based on their clinical course. They may also be symptomatic or asymptomatic. The clinical subgroup: acute/chronic, may be further subdivided into myeloblastic and lymphocytic variants such as acute lymphoblastic leukaemia (ALL), AML, CLL and chronic myeloid leukaemia (CML). However, a variant called bi-phenotypic leukaemia exhibits features of acute and chronic leukaemia.[3]

The ophthalmic manifestations may occur before the systemic disease or along the course of the disease process, or from an isolated focal relapse after complete recovery from systemic leukaemia or even from chemotherapeutic agents.[3],[4],[5] When present, they may be associated with significant ocular morbidity and vision loss and have critical implications for the natural course and survival prognosis of systemic leukaemia. Ocular disorders have been seen in 30%–90% of leukaemic cases,[6],[7],[8],[9],[10] and it has been found that up to 90% of patients with leukaemia will have fundal involvement at some point in their disease process.[11],[12] Back in the days before bone marrow biopsies, ophthalmologists were routinely consulted to assist in the diagnosis of leukaemia by fundoscopy looking out for leukaemic retinopathy.

Leukaemia may directly infiltrate the ocular structures of the eye or indirectly arise from systemic secondary haematologic changes, opportunistic infections, complications from cytotoxic drugs, total body irradiation or effects of allogeneic bone marrow transplantation.[13],[14],[15],[16] Ocular involvement is more commonly seen in acute than the chronic forms, and virtually, any ocular structures may be involved. The common posterior segment findings include retinal haemorrhages, cotton wool spot and retinal haemorrhages with white centre referred to as Roth spots. Peripheral retinal neovascularisation is an occasional feature of chronic myeloid leukaemia, and choroidal deposits in chronic leukaemia may occur giving rise to a 'leopard skin' appearance of the retina. Optic nerve infiltration could also be seen leading to proptosis and vision loss.[8] Other rare ocular features of leukaemia include orbital involvement especially in children and cranial nerve palsies. In the anterior segment, there may be spontaneous subconjunctival haemorrhage, iris thickening, iritis, hyphema and pseudohypopyon.[17]

Knowledge of the ocular manifestations of leukaemia is important not only because of the frequency with which changes are seen but because the eye often reflects the disease state of illness, and once identified, prompt referral, investigations, early treatment can be instigated, visual loss may be averted and a life may be saved. However, these manifestations are often overlooked because of the underestimation of the magnitude of the ocular sequelae which maybe blinding, resulting from leukaemia. This study sought to give an additional view of the ocular disorders in patients living with leukaemia at two tertiary hospitals in Lagos, Nigeria, compared with age- and sex-matched controls.


  Patients And Methods Top


This was a clinic-based comparative multicentric study conducted at Lagos University Teaching Hospital and Lagos State University Teaching Hospital over a 9-month period from May 2012 to January 2013. Ethical approval was obtained from the teaching hospital ethics and research committee with assigned number ADM/DCST/HREC/413 and approval dated from 4 April 2012 to 4 April 2013. Written informed consent was obtained.

Patients (cases) were recruited from the haematology clinics during the study period. The diagnosis and classification of leukaemia was based on bone marrow aspiration cytology. The controls were relatives of patients who escorted these patients to the eye clinics for ocular emergencies whom themselves had no complaints. These were age and sex matched with the cases based on the inclusion and exclusion criteria.

Inclusion criteria for cases were as follows

All newly diagnosed patients (males and females) not on any previous treatment at the haematology clinics over 16 years of age confirmed to have leukaemia via bone marrow aspiration cytology with no systemic comorbidities (diabetes, hypertension, sickle cell disease, human immunodeficiency virus/acquired immunodeficiency syndrome HIV/AIDS, lymphomas and other blood dyscrasias).

The inclusion criteria for controls were as follows

Individuals over 16 years of age (age and sex matched with the cases) who escorted patients to the eye clinics for ocular complaints/emergencies whom were not directly related to the cases and without systemic comorbidities (diabetes mellitus, hypertension, sickle cell disease, HIV/AIDS, lymphomas, other bleeding disorders like haemophilia).

Exclusion criteria used were as follows

Individuals with other systemic problems such as hypertension, diabetes, human immune deficiency virus/AIDS, sickle cell disease, lymphoma and other bleeding dyscrasias. Others include individuals who are already receiving treatment for leukaemia and individuals who were related to the cases.

The sample size for this study was calculated using an accepted formula for comparative studies [18] and allowing for 20% attrition. With a standard normal deviate at 95% confidence level set at 1.96. The prevalence of an attribute present in the population P was taken as 14.9% = 0.149, based on a previous study in Nigeria that reported a prevalence of 14.9% for ocular morbidity amongst leukaemic patients. Thus, the minimum sample size n calculated with the above parameters was 32, and following the inclusion of 20%, the sample size came to 40. The sampling technique was a convenient sampling of consecutively consenting cases and controls who met the study criteria until the target sample size was met.

The study was carried out by a team that comprised of an ophthalmologist (Lead Author), one resident doctor in ophthalmology and an ophthalmic nurse. Following enumeration, all cases and controls had detailed ocular evaluation that included visual acuity testing with Snellen's chart and the anterior segment structures examined with a slit lamp biomicroscope. The structures of the anterior segment examined were the conjunctiva, cornea, sclera, anterior chamber, iris, pupil and the crystalline lens. This was followed by dilated examination of the posterior segment. The eyes were dilated with instillation of tropicamide, and the examination of the posterior segment structures was done with the use of binocular indirect ophthalmoscope, 78D lens and a slit lamp biomicroscope. The structures of the posterior segment examined were vitreous, optic nerve head, macula and the peripheral retina.

The data were entered into database and analysed using the IBM Statistical Package for the Social Sciences Software version 17.0 (IBM SPSS, IBM Corp., Armonk, NY, USA). A descriptive analysis of data to determine the frequency of ocular manifestations, age and sex distribution was done. Means were compared using student t-test. Factors that were found to be significant in the bivariate analysis were introduced in a multivariate logistic regression model for risk factors for all individuals. P < 0.05 was considered to be significant for these analyses, and Fisher's exact P was used where a cell had a count of <5.


  Results Top


A total of 80 participants (40 cases and 40 controls) were recruited for the study. There was no statistical difference in age between the cases 45.20 years (standard deviation [SD] ± 16.13) and controls 45.35 years (SD ± 15.76). There were 20 males–20 females in both study groups. Types of leukaemia in the cases included chronic myeloid leukaemia in 16 (40%), CLL in 11 (27.5%), acute lymphocytic leukaemia in 10 (25%), acute myeloid leukaemia in 2 (5%) and only one case (2.5%) of biphasic leukaemia (acuteonchronic). See [Figure 1]
Figure 1:Frequency of types of leukaemia among the cases studied

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The presenting visual acuity was <6/18 in 33.8% of cases as compared to 21.3% of the control group. Leukaemic-related ocular findings including retinal infiltrates, Roth spots, perivascular sheathing, disc oedema, periocular oedema, subconjunctival haemorrhage and proptosis were found in 70% of the cases [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]. None of the controls had these findings. These have been postulated to possible attribution to leukaemia in literature [6],[7],[8],[9],[10],[19] Worthy of note is the fact that while eight of the leukaemic patients had periorbital oedema, none of the controls did [Table 1].
Figure 2: Subconjunctival haemorrhage (Anterior segment finding)

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Figure 3: Fundus photograph of the patient with retinal vein tortuosity

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Figure 4: Fundus photograph of the patient with Roth spots and intraretinal haemorrhage

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Figure 5: Chronic myeloid leukaemia patient with exudative retinal detachment

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Figure 6: Patient fundal findings Roth spots and cotton wool spots

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Table 1: Anterior segment lesions in the cases and controls

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The relationship between having leukaemia and developing posterior segment lesions such as retinal infiltrates, Roth spots, perivascular sheathing, retinal vascular tortuosity, intraretinal haemorrhage and disc oedema with the exception of cotton wool spots were found to be statistically associated with the development of leukaemia [Table 2].
Table 2: Posterior segment lesions in the cases and controls

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CLL appears least likely to lead to ocular sequelae with the odds being 0.217 [Table 3].
Table 3: Variants of leukaemia and leukaemic-related ocular manifestations (80 eyes)

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  Discussion Top


This study buttresses the importance of a complete ophthalmological evaluation in the care and follow-up visits in patients with leukaemia. Among the cases, 70% (56 eyes) had leukaemic-related ocular findings; this is comparable to the prevalence of leukaemic ocular findings, i.e. 69.0% reported in Ethiopia by Alemayehu et al.,[9] and also similar to the 77.8% prevalence reported by Eze et al.,[20] but differed markedly from the 14.9% reported by Omoti et al.,[21] 35.4% reported by Reddy et al.[8] and 39.0% by Schachat et al.[22] The difference in patient selection criteria, racial variation and number of patients screened could be adduced as possible reasons for the disparity in reported figures.

The leukaemic-related anterior segment findings identified were either present in one or both eyes and are similar to those previously reported in other study.[21] The causes of blindness among the cases studied were from exudative retinal detachment [found monocularly in a patient with CML [Figure 5] and optic disc oedema [in a young man with ALL [Figure 2]; these findings were as found in a similar study.[21] These cases died shortly after presentation. The only case of monocular blindness seen in the control group was from mature cataract.

Of all the anterior segment findings identified in this study, the most common was periorbital oedema. This has been postulated to be one of the leukaemic-related findings. This finding was similar to a study done in the United States;[23] however, the occurrence in the US was linked to drug toxicity.

Our study reported periocular oedema as the most common ocular finding among the cases seen, while Omoti et al.[21] reported proptosis and Eze et al.[20] found conjunctiva pallor and subconjunctival haemorrhage as the most common ocular finding. The difference between these studies is difficult to explain, but subtle difference in racial and diagnostic tools could be implicated. Periocular oedema and proptosis are in line with what is expected of Africans,[24] with a higher prevalence of leukaemic ophthalmopathy. Interestingly enough while pterygium was found in 6 of the study participants, none of the eyes of cases studied had pterygium. Could there be a protective factor from leukaemia? Or could it be due to the fact that patients living with leukaemia with associated poor health tend not to engage in a lot of outdoor activities hence less exposure to ultraviolet radiations from sunlight? Surely, a larger study could explain this.

Potentially blinding complications found in this study, included proptosis, cataract, disc oedema, optic atrophy, glaucoma, maculopathy and retinal detachment. These were seen in 37 patients (97.5%), of which leukaemic-related blinding complications occurred in 18 cases and the rest had blinding complications not known to be directly related to leukaemia. Patients with potentially blinding complications were given appointment to be followed up at the eye clinics. A case of monocular blindness from exudative retinal detachment was seen in a patient with CML variant which is similar to another study.[21] The only case of blindness was seen in a CML patient who had bilateral exudative retinal detachment [Figure 5]. Retinal detachment has also been reported in CLL in other studies.[25],[26] Posterior segment sequelae including retinal detachment has been said to result from effects of infiltration of circulating antibodies.[27]

Limitations of this study

The study had limitation in view of the small sample size, as leukaemia seems an uncommon disease, especially the acute types. This makes comparison among different types of the disease difficult. Furthermore, the presentation of patients to the two hospitals was erratic, due to the unpredictable pattern of presentation making it difficult to track them for evaluation.


  Conclusion Top


There is need for development of a standard referral protocol between the haematology clinic and the eye clinic so that leukaemia patients can have periodic evaluation. This is to reduce the burden on patients living with leukaemia needlessly going blind in addition to their systemic setback.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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