Dr. Ruchir Mehta, M13882, Dr. Padmamalini Mahendradas, Dr. Ashwin Mohan, Dr. Poornachandra B, Dr. Rohit Shetty
Introduction
Tuberculosis (TB) is a disease caused by the acid-fast bacillus (AFB) Mycobacterium tuberculosis. India accounts for nearly 1/3rd of global burden of TB. 1.4% of persons with PTB develop ocular manifestations but many patients with ocular TB have no evidence of PTB. Criteria for establishing a diagnosis of ocular TB are not well established so the epidemiology of ocular TB is less certain than for TB.
Oxygen is important for the normal physiology and metabolism in the body. The retina has the highest metabolic demands of any tissue in the body with the photoreceptors having the highest demand in the retina. [1] Inadequate delivery of oxygen or altered utilization of oxygen can either trigger disease or be a marker for underlying disease activity respectively. [2–5]
Ocular inflammation would result in increase of blood flow to the affected part or the entire globe with increased consumption of oxygen by the tissue and reduced oxygen saturation of haemoglobin in the affected part.
Hemoglobin bound to oxygen has differential absorption of light at different wavelengths. This is the basic principle used in dual wavelength oximetry. Fundus photographs at 2 different wavelengths are taken and the relative oxygen concentration can be determined using photo-spectrometry. [6,7] Jani et al [8] in their work state that this machine is based on a similar principle as the finger pulse oximeter.
On literature review we did not find any study which has tried to study oxygen saturation of retinal vessels in ocular inflammation
In our study, we try to compare oxygen saturation of retinal vasculature in cases suffering from active ocular tuberculosis to age matched and sex matched group of normal eyes. Our objective is to show that this can help in determining the activity of the disease process and aid in management for the same.
Materials and Methods
This is a cross sectional observational case series of 20 eyes of 15 consecutive patients presenting to the Ocular Immunology and Uveitis department at Narayana Nethralaya, Bangalore, diagnosed with ocular tuberculosis were enrolled in the study. The diagnosis of these conditions was made based on the presentation, clinical findings and laboratory diagnosis. The study followed the tenets of Helsinki. The Ethics Committee and Institutional Review Board of Narayana Nethralaya approved the study. All patients gave a written consent for the study.
All patients underwent a complete ophthalmic examination. These included measurement of the best-corrected visual acuity (BCVA), anterior segment examination, measurement of the intraocular pressures and a fundus examination. Patients younger than 18 years of age, smokers, with a previous history of trauma, nystagmus and poor media clarity were excluded from the study.
The patients were diagnosed as ocular tuberculosis and they were compared with age matched normal chosen from our normative database.
Image Acquisition
Following dilation with 10% tropicamide and 1% phenylephrine, all patients underwent dual wavelength photo-spectrometric Oximetry (Oxymap T1 retinal oximeter, Oxymap, Reykjavik, Iceland).
The initial images were obtained after the patients were allowed to rest for 5 minutes to eliminate exercise-induced fluctuations in readings. Resting blood pressure and pulse oximetry (Silicon Labs) readings were measured in all patients. None of the subjects had consumed caffeine within 2 hours of the examination. The aiming light was set at the lowest setting, flash intensity was 50W, small aperture and large pupil settings were applied to the Topcon TRC 50DX Fundus camera.
One experienced photographer obtained standardized images for all the subjects. We obtained 2 images per eye of 50˚ field that were disc centred in all subjects. (Fig 1) We used the OxymapAnalyser version 2.5.1. Eyes with automatic image quality less that 7.5 were excluded.
To confirm inter-rater agreement, we had the images analysed by another observer. We found strong agreement in the measured values obtained by the two observers, so for data analysis only information from our first observer has been used.
Statistical Analysis
Statistical analysis was done using IBM SPSS v22.0. Inter observer agreement was calculated using intra-class correlation coefficient that tested for consistency. All parameters were tested for normality using the Shapiro-Wilk Test. Parametric data was analyzed using the One-way ANOVA with the Turkey test for post-hoc analysis. Non-parametric data was compared using the Kruskal-Wallis test and the Mann-Whitney U test for the post-hoc analysis. Chi-square test was used for nominal data.
Results
From a total of 22 patients, 15 were included. 7 were excluded due to inadequate image quality. There were a total of 20 eyes with (5 bilateral, 10 unilateral) and 42 controls (all unilateral). 5 patients had panuveitis, 4 patients had retinal vasculitis, 3 had serpiginous-like choroiditis, 2 had multifocal choroiditis and 1 had intermediate and anterior uveitis.
Agreement
The intraclass correlation coefficient for consistency for single and average measures respectively was 0.868 and 0.930 for arteriolar saturation; 0.875 and 0.944 for venous saturation; 0.862 and 0.926 for arteriolar diameter and 0.823 and 0.903 for venous diameters. These values indicate almost perfect agreement.
Demographics
The average age in the ocular tuberculosis group was 33.85 ± 12.6 years and the control group was 36.0 ± 13.7 years. We had 13 male eyes and 7 female eyes in ocular tuberculosis group & 16 male eyes and 26 female eyes in normal group. No significant differences were found in the age or sex distribution.
Global Saturations and Diameters
Although the venous oxygen saturation in eyes with ocular tuberculosis was less as compared to the normal group, the arteriolar and venous saturation did not show any significant differences between the two groups. The arteriolar saturations in the ocular TB group were higher than controls (p = 0.770). The venous saturations were lower in the ocular TB group (p = 0.161). The AVSD was higher in the ocular TB group significantly different from controls (p<0.05). The arteriolar and the venous diameters were not significantly different between the groups (p=0.646, p=0.333 respectively).
Discussion:
The hemoglobin oxygen saturation in the venous blood was less in patients with ocular tuberculosis and the arteriovenous difference of hemoglobin oxygen saturation was statistically significant between the two groups.
Hanioka T et al. [9] studied oxygen saturation of hemoglobin at each site by tissue reflectance spectrophotometry in 10 patients with 40 inflamed gingival sites. They showed that reversible changes resulting in increase in the local hemoglobin concentration and oxygen saturation were associated with decreasing gingival inflammation in human subjects. We found no such studies for ocular inflammation.
The method of determining disease activity in uveitic conditions depends as of now on subjective method of grading vitreous and anterior chamber inflammation, the ability of the clinician to remember or properly document the same at every visit, clinical expertise/ experience of the clinician, tests both invasive and non-invasive like OCT and FFA. This can lead to lot of discrepancies and needless continuation/ excess of treatment.
The limitations of our study are that we do not have quadrant wise saturation levels, instead we have a global saturation measurement which is average of all the arteries and veins near the disc margin. The current approach of our study excludes vessels narrower than 8 pixels or 74 μm, hence we cannot comment on vessels that were narrower than this cutoff and therefore not measurable.
Conclusion:
Retinal oximetry adds a new dimension to determining the disease activity. It gives an objective method of understanding and quantifying the disease process which can add to the clinician’s observation and guide the clinician in the management to improve the venous oxygen saturation and decrease in AV oxygen saturation difference in ocular inflammation.
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