|Year : 2019 | Volume
| Issue : 11 | Page : 1570-1575
Transorbital sonographic measurement of optic nerve sheath diameter among HIV-Positive patients in Northwestern Nigeria
PI Ebisike1, SG Habib1, S Hassan1, MA Suwaid2, MS Hikima2, MK Saleh2, U Jibo2, L Yusuf2
1 Department of Ophthalmology, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Radiology, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Submission||03-Dec-2018|
|Date of Acceptance||15-Jun-2019|
|Date of Web Publication||13-Nov-2019|
Dr. M A Suwaid
Department of Radiology, Bayero University/Aminu Kano Teaching Hospital, Kano
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Human immunodeficiency virus (HIV) is a pandemic disease affecting all regions across the globe and Nigeria having the second highest prevalence worldwide. Highly active antiretroviral therapy (HAART) has profound negative effect on the optic nerve even though (HAART) has improved the health status of the affected individuals and overall reduction in mortality. Imaging modality especially ultrasound has a great role in the assessment of the optic nerve because of its availability, affordability, and easy operability with reliable sensitivity. Subjects and Methods: This cross-sectional study was conducted at the Department of Radiology and Ophthalmology, AKTH, Kano, from October 2017 to June 2018. A total of 143 consenting HIV-positive adults age 18–60 years on HAART were recruited. Optic nerve sheath diameter (ONSD) of each eye was measured using 11–14 MHz linear transducer. Ethical approval was obtained from the ethic and research committee of the hospital. Results: The mean ONSD value of the right eye was 3.49 mm ± 1.04 standard deviation (SD) and 3.55 mm ± 1.11 SD for the left eye. The optic nerve diameter was found to be larger on the left eye and increased slightly with age (P < 0.05). There was nonsignificantly higher values of ONSD among female (3.59 mm ± 1.12 SD) when compared with males (3.332 mm ± 0.878) with P value >0.005. Conclusion: ONSD values among HIV-positive patients are significantly higher in the left eye and among female subjects. Also, patients with HIV on HAART have thicker optic nerves when compared with general population in Kano, Nigeria.
Keywords: HAART, HIV, optic nerve diameter, ultrasound
|How to cite this article:|
Ebisike P I, Habib S G, Hassan S, Suwaid M A, Hikima M S, Saleh M K, Jibo U, Yusuf L. Transorbital sonographic measurement of optic nerve sheath diameter among HIV-Positive patients in Northwestern Nigeria. Niger J Clin Pract 2019;22:1570-5
|How to cite this URL:|
Ebisike P I, Habib S G, Hassan S, Suwaid M A, Hikima M S, Saleh M K, Jibo U, Yusuf L. Transorbital sonographic measurement of optic nerve sheath diameter among HIV-Positive patients in Northwestern Nigeria. Niger J Clin Pract [serial online] 2019 [cited 2022 Jan 25];22:1570-5. Available from: https://www.njcponline.com/text.asp?2019/22/11/1570/270868
| Introduction|| |
Human immunodeficiency virus (HIV) infection has become a global public health issue. In 2016, estimated 36 million people are infected with HIV with a global prevalence of 0.8% among adults. Nigeria is the second country in the world with the largest number of people living with HIV/acquired immunodeficiency syndrome (AIDS) having a prevalence of 2.9%. Despite the inherent challenges, there has been a dramatic increase in the number of people receiving antiretroviral therapy (ART) with an estimate of about 3 million people presently receiving ART in low- and middle-income countries leading to a decline in morbidity and mortality associated previously with HIV, hence increase in life expectancy of the patients.,, Highly active antiretroviral therapy (HAART) has also caused a significant decline in the incidence of ocular manifestations of HIV, like cytomegalovirus retinitis, necrotizing retinitis, kaposis sarcoma, and retinal detachment, among the major causes of visual loss in patients with HIV.
The use of HAART therapy among patients with HIV has led to increased exposure to the potential risks of drug toxicity and side effects of HIV treatment in addition to the burden of the disease. Approximately 24% of patients who initiate HAART will need to change a medication because of adverse effects. These effects include dyslipidemias, diabetes mellitus, insulin resistance, lipodystrophy syndrome, and lactic acidosis associated with NRTI mitochondrial toxicity. However, specific ocular manifestations that have been reported among HIV-positive patients on HAART include immune recovery vitritis or immune recovery uveitis, epiretinal membrane, vitreal haze, cystoid macular edema, optic nerve head edema, herpes zoster ophthalmicus, and retinovascular disease in which there are retinal infarcts.,, In neuroretinal disorder (NRD) in which there is depletion of retinal nerve fiber layer despite the use of ARTs, the patients suffer retinal damage and loss of vision., There are also abnormalities of color vision and contrast sensitivity leading to the complex called HIV-associated NRD., In this condition, patients who have not suffered opportunistic infection throughout the course of the disease become predisposed to development of NRD. In patients with HIV positivity, there is a possibility of structure of the optic nerve head changing over a period of time which may be associated with development of NRD.
The optic nerve is the second cranial nerve, extending from the optic disc to the optic chiasm. It is a posterior extension of the nerve fiber layer with axons originating from the ganglion cell layer of the retina composed of about 1 million fibers. The nerve has a length of about 47–50 mm and it is divided into four parts. The ocular part passes through the sclera, choroid, and finally emerges as the optic disc. It has a length of 1 mm and a diameter of 1.5 mm which enlarges to a diameter of 3 mm behind the sclera where the nerve acquires a myelin sheath and has three meningeal layers covering its subarachnoid space continuous with that of the brain., The function of optic nerve is to carry the electrical impulses from retina to brain, and thus it can also be termed as the nerve of vision.
Imaging of the optic nerve head becomes important in these patients because there may be changes due to NRD or other ocular diseases associated with immune recovery process in patients on HAART. There are many imaging techniques for evaluation of the optic nerve head, but ultrasonography is a more accessible, safe, noninvasive, easy to learn, fast, and relatively cheap method of evaluation of both anterior and posterior ocular structures. The retrobulbar optic nerve sheath diameter (ONSD) can be measured at a position 3 mm posterior to the globe, where ultrasound contrast is greatest with more reproducible results, and anatomically, the anterior aspect of the nerve is most distensible. Moreover, the fluid nature of the globe and its superficial location along with the use of high frequency transducers in ultrasound machines make it possible to clearly visualize anatomy and pathologic conditions affecting the eyes.
There are few studies on optic nerve diameter in patients with HIV among sub-Saharan Africans, hence the need to determine ONSD among this category of patients on HAART.
The aim of this study is to determine the ONSD using orbital sonography among patients with HIV on HAART in this environment and correlating the measured ONSD with age and gender of the study subjects. Also to note whether there is any significant difference compared with previous studies done on normal individuals.
| Subjects and Methods|| |
This cross-sectional designed study was carried out following Aminu Kano Teaching Hospital Research ethics committee approval and was conducted in the Department of Radiology and Ophthalmology of the hospital from October 2017 to June 2018. A total of 143 consenting adult patients age 18–60 years who were HIV-positive and receiving HAART in AKTH for at least more than 6 months were enrolled in this study. All subjects had no visual loss or history of ocular surgery/ophthalmic diseases, such as ocular tumors or traumas. Other exclusion criteria were <18 years of age, history of glaucoma or current medications that might have affected cerebrospinal fluid pressure, poisoning by drugs or substances that cause impaired consciousness, endocrine disorders (such as hypoglycemia or hyperglycemia, hypothyroidism, or hyperthyroidism), age, sex, and duration the patients were on treatment with HAART.
ONSD measurement was performed by a single radiologist using a Mindray SP Digital Ultrasound Imaging System (Model DP-8800Plus; Mindray Biomed electronics, Shenzhen, China) with 7–12 MHz high-frequency transducer in the Radiology Department of AKTH. Patients were examined in the supine position with a closed eyelid and maintaining gaze at the scanning room ceiling. Both globes were scanned in longitudinal, transverse, and craniocaudal planes through the eyelid, and then optic disk of the eye was viewed and ONSD measurements were performed in transverse and sagittal planes by identifying the hypoechoic optic nerve and the widest visible retrobulbar ONSD was measured at a point 3 mm posterior to the optic disk of the globe using an inbuilt electronic caliper to the nearest millimeter [Figure 1]. All measurements were triplicated for each globe and the average was entered as the recorded ONSD. All measurements were performed by the same observer to eliminate interobserver variations.
|Figure 1: Sonogram of the left globe showing ONSD at a point 3 mm from the optic disc|
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All data were analyzed using IBM Statistical Package for Social Sciences (version 23.0; SPSS, Chicago, IL, USA). A P value of <0.05 was considered statistically significant. Age, gender, ONSD values, and the difference between ONSD values of both eyes of patients were compared. The mean ONSD value of left eye (LE) and right eye (RE) was used for statistical analysis. An ONSD value less than 5 mm for both eyes was considered normal. Kolmogorov–Smirnov test was used to determine the normality of the distribution of the continuous and discrete quantitative variables. Descriptive statistics were expressed as mean ± standard deviation (SD) or median (minimum–maximum) for continuous and discrete quantitative variables and percentages (%) for categorical variables. Categorical variables were analyzed using Chi-square test; parametric data were analyzed using Student's t-test and nonparametric data were analyzed using Mann–Whitney test.
| Results|| |
The sociodemographic information of the subjects were analyzed based on age and sex. A total number of 143 subjects with 286 eyes were measured [Table 1]. A majority of the subjects were females [89 (62.2%)] with a ratio of male: female = 1:1.6 [Table 2]; [Figure 2].
|Table 1: Mean and standard deviation of age and optic nerve diameters of the left and right eyes|
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The subjects' mean age was 37.24 ± 8.16 years with a range of 19–60 years [Table 1]. The highest number of the subjects falls within the age limits of 31–40 years (40.6%) and the lowest within 10–20 years (2.8%).
The mean optic nerve diameter of the RE was 3.49 ± 1.04 mm with a range of 1.70–6.50 mm when compared with the mean of LE 3.55 ± 1.11 mm and range of 2.00–6.40 mm [Table 1]. The mean total of the optic nerve diameters of both eyes was 3.52 ± 1.07 mm with range of 1.70–6.50 mm [Table 1].
Also, [Table 3] showed that the mean of the optic nerve diameters of the LE is greater than that of the RE. The test statistics using one-sample T-test analysis showed a statistically significant difference between the mean value of the optic nerve diameter of the RE and LE (P = 0.000) and also between age and the optic nerve diameter (P = 0.000).
|Table 3: Mean ONSD for the right, left, and both eyes in females; right, left, and both eyes in males|
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The highest value of the optic nerve diameters was 6.5 mm when compared with the lowest value of 1.7 mm [Figure 3].
|Figure 3: The normal distribution curve of the optic nerve diameters with age groups|
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| Discussion|| |
We decided to undertake this study because Nigeria is the second country in the world with the largest number of people living with HIV/AIDS having a prevalence of 2.9%, thus the burden of HIV infection in Africa is high. In 2006, the World Health Organization proposed that 2.3 million children were living with HIV infection mostly acquired through mother-to-child transmission, and about 90% of them live in sub-Saharan Africa. We therefore feel the need to check the pattern of ONSD in this group of patients.
A majority of the subjects in this study were females comprising about 62.2% when compared with males that constitute 37.8%, thus a ratio of male:female = 1:1.6. Globally, women comprise about 52% of the total number of people living with HIV. Therefore, our finding of more women with HIV AIDS in this study is therefore consistent with documented literature.
Many other studies carried out in similar subjects showed that increased optic nerve diameter is associated with elevated cerebrospinal fluid pressure and raised intracranial pressure (ICP)., Various clinical conditions are known to cause increased ICP in patients with HIV/AIDS. These include cryptococcal meningitis, toxoplasma encephalitis, and non-Hodgkin's lymphoma. The increase in optic nerve diameter observed in this study therefore points to the possibility of the presence of some degree of raised ICP in these patients from one or more of the well-established causes as mentioned above.
Previous studies have shown no difference between the mean diameters of the optic nerve on right and left sides. The variation in ONSD observed in this study between the right and left sides therefore may point to intracranial pathologies which often are not symmetrically distributed, leading to increase in diameter on the left relative to the right as observed in this study.
Studies of ONSD using ultrasound have not been done as far as our limited literature search is concerned. However, study of retinal fiber layer thickness and cross-sectional area among patients with HIV by Daniel et al. in adult HIV-positive subjects in California, USA, shows minimal decrease in measured dimensions when compared with normal healthy controls. This is at variance with our findings. This may be due to differences in methodologies whereby they used confocal scanning laser ophthalmoscope, while we used high-resolution ultrasound scanning technique.
According to Ismail, in his study of normal ONSD in Kano Northwest Nigeria, individuals from different ethnic groups in different countries and continents vary in characteristics, such as skin color, facial structure, and height. In this context, the sonographic reference value is, therefore, beneficial as it provides the basis for monitoring patients with raised ICP. This is why our finding of mean total of the optic nerve diameters of both eyes of 3.52 mm is slightly higher than the findings by Ismail of 3.36 mm. The increase in ONSD in patients with HIV on HAART may be an early presentation of optic neuropathy as previous studies have reported optic neuropathy in patients with HIV on antiretrovirals such as zidovudine, stavudine, and zalcitabine.
Aside from the raised ICP, HIV has been found in all ocular fluids: tears, aqueous, and vitreous, mononucleated white blood cells and HIV-infected macrophages which may act by releasing neurotrophic factors, enzymes, or cytokines, or by directly releasing virions, enveloping glycoproteins, or inflammatory mediators. The elevated levels of cytokines, particularly TNF-α, interleukin-1, and interleukin-2, have been reported in the serum of patients with AIDS and they play an important role in promoting HIV infection of eye and central nervous system including the optic nerve leading to inflammation and eventual rise in ICP and increase ONSD.
The effect in the diameter of ONSD in HIV infection is as a result of microvascular changes in several vascular beds: conjunctiva, optic disc, and, most commonly, the retina. HIV retinopathy is seen in 40%–100% of infected patients and has been found in 89% of autopsy specimens. HIV vasculopathy is characterized by microaneurysms, telangiectasia, retinal hemorrhages, and cotton wool spots. This eventually leads to ischemia and in the early stage may lead to inflammation and release of toxins that may cause increase in ONSD.
The findings in this study show an increase in the optic nerve diameter which is at variance with some other studies which showed reduction in the diameter as a result of optic atrophy and eventually reduction in ONSD due to AIDS-associated primary optic neuropathy due to axonal loss. This may be because the subjects in the present study are stable and are already on HAART.
The study by Ismail  in Kano Northwestern Nigeria did not find any difference in the ONSD measurement between males and females, just like this index case. This study, however, showed that the optic nerve diameters of the LEs are greater than the REs as seen by their means and SDs. The test statistics using one-sample T-test analysis showed a statistically significant difference between the mean value of the optic nerve diameter of the RE and LE (P = 0.000). This may be because of the already established fact that some clinical conditions are known to cause increased ICP in patients with HIV/AIDS and they affect the ONSD unevenly.
The ONSD measurement in different age groups has a pattern that showed a steady increase in the ONSD upto the age of 40 years before dipping at 41–50 years and rise again. This pattern might be explained by the fact that ONSD increases with age and also due to inflammation from the HIV. At 40–50 years, however, there must have been demyelination and also the chronicity of the infection before the start of the HAART. The rise again at 40–50 years might have been the effect of HAART on the clinical conditions that normally occurs in HIV.
In conclusion, the burden of HIV infection is real in Nigeria and West African subregion. Similarly, the use of HAART therapy has increased the life span of the patients with HIV aside from increased exposure to the potential risk of drug toxicity. All this leads to ocular changes which are important to document.
The mean ONSD was found to be 3.52 ± 1.07 mm which as documented by others is slightly thicker than in normal subjects. We also found that mean optic nerve diameter of the LE is greater than the right but no difference between the sexes. The highest ONSD was 6.5 mm and lowest was 1.7 mm.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]