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   Table of Contents      
ORIGINAL ARTICLE
Year : 2018  |  Volume : 66  |  Issue : 11  |  Page : 1554-1557

Changes in corneal thickness in patients with high-altitude pulmonary edema after systemic oxygen therapy


1 Centre for Sight, New Delhi (Formerly Consultant, Army Hospital R and R, New Delhi), New Delhi, India
2 Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Community Medicine, Army College of Medical Sciences, New Delhi, India

Date of Submission24-Apr-2018
Date of Acceptance31-Jul-2018
Date of Web Publication25-Oct-2018

Correspondence Address:
Dr. Arun Kumar Yadav
Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_642_18

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  Abstract 


Purpose: High-altitude pulmonary edema (HAPO) is an acute medical emergency occurring typically in lowlanders, who ascend rapidly to heights of 3000 m or more. It presents with marked dyspnea on exertion, fatigue with minimal-to-moderate effort, prolonged recovery time, and dry cough with manifestations of cyanosis, tachycardia, tachypnea, and temperature which generally does not increase beyond 38.5°C. The condition may be fatal if not treated in time with supplemental oxygen or hyperbaric oxygen or rapid descent to lower altitude. There is paucity in literature on changes in corneal thickness in HAPO. The effect of continued oxygen therapy on corneal thickness has also not been studied in detail. Hence, this study was conducted at high altitude among physician-confirmed HAPO cases. Methods: A case–control study was conducted at an altitude of 11,400 feet. Cases were patients suffering from HAPO and controls were patients admitted in hospital for low back pain, fractures, and minor surgical procedures. Central corneal thickness (CCT) was measured with an ultrasound pachymeter on day 1 of hospitalization and every day of hospital stay. Systemic oxygen concentration was also measured daily. Results: There was no statistically significant difference in corneal thickness between two groups at the onset of illness, but a significant decrease in CCT was found in both right and left eyes in HAPO cases when oxygen levels were increased by giving supplemental oxygen. Hierarchical modeling showed a decrease in 1.3 μm in CCT with one unit increase in oxygen mmHg in cases. Conclusion: The findings of statistically insignificant difference in CCT between HAPO cases and controls and a decrease in CCT in HAPO cases on being treated with systemic oxygenation are points to ponder about.

Keywords: Case–control study, central corneal thickness, high altitude, high-altitude pulmonary edema, oxygen therapy


How to cite this article:
Patyal S, Yadav AK, Kotwal A. Changes in corneal thickness in patients with high-altitude pulmonary edema after systemic oxygen therapy. Indian J Ophthalmol 2018;66:1554-7

How to cite this URL:
Patyal S, Yadav AK, Kotwal A. Changes in corneal thickness in patients with high-altitude pulmonary edema after systemic oxygen therapy. Indian J Ophthalmol [serial online] 2018 [cited 2019 May 21];66:1554-7. Available from: http://www.ijo.in/text.asp?2018/66/11/1554/244073



High altitude attracts large numbers of people for sports, pleasure, and work. Barometric pressure at high altitude is reduced and may result in a number of diseases. Some of the diseases may be fatal, if not timely diagnosed or treated. Among the three commonest systemic diseases affecting individuals who ascend to high altitude are acute mountain sickness (AMS), high-altitude pulmonary edema (HAPO), and high-altitude cerebral edema (HACO).

HAPO is an acute medical emergency occurring typically in lowlanders, who ascend rapidly to heights of 3000 m or more.[1] HAPO can also occur in highlanders returning to high altitudes after living in low altitudes for some time. “Re-entry HAPO is also a known entity and is very important for military personnel who make several sojourns in low and high altitudes during their lifetime and during their tenure in high altitude.”[1] Its incidence is variable, ranging from 0.01% to 0.1% in the rocky mountains of Colorado to 15% of unselected population of Indian soldiers air lifted to 5500 m.[2] This condition may affect susceptible individuals at high altitudes or can occur in individuals who exercise soon after ascent at high altitude without sufficient acclimatization. It may manifest early, as within a few hours of stay in high altitude or later, presenting with marked dyspnea on exertion, fatigue with minimal-to-moderate effort, prolonged recovery time, and dry cough. Manifestations of HAPO can be cyanosis, tachycardia, tachypnea, and temperature which generally does not increase beyond 38.5°C. The condition may be fatal if not treated in time with supplemental oxygen or hyperbaric oxygen or rapid descent to lower altitude.[1]

The eye too is affected by high altitude in many ways.[3] Dry eyes, photo keratitis, high-altitude retinopathy, pterygium, cataract, and vascular occlusions are known to occur in a large number of people on ascent to high altitude. Temporary increase in corneal thickness and intraocular pressure also occurs on ascent to higher reaches.[4],[5] This increase in corneal thickness does not affect vision.[3]

It has also been found that an increase in corneal thickness depends on the period of acclimatization, with a shorter period of acclimatization resulting in greater corneal thickness. Individuals with more AMS-related symptoms have thicker corneas due to their higher susceptibility to hypoxia.[6]

Review of literature shows no reference of changes in corneal thickness in HAPO. Neither is there any correlation between amount of corneal thickness and oxygen level in the body. This study was conducted at 11,400 feet in 1 year to evaluate corneal thickness in patients with physician-proven cases of HAPO and compare it with age-matched controls (other patients in the same hospital) and to study the effects of systemic oxygenation on corneal thickness in patients with HAPO.


  Methods Top


A hospital-based, case–control study was conducted at 11,400 feet, with cases being patients suffering from HAPO while residing in high altitude (9000–20,000 feet above mean sea level). Patients who developed HAPO at remote locations with poor medical facilities were transferred to the tertiary care center at 11,400 ft. Inclusion criteria were physician-confirmed cases of HAPO admitted to hospital, males between 20 and 50 years. Persons with preexisting ocular disorders (i.e., keratopathies, tear film abnormalities) and previous ocular surgeries and any other systemic illnesses were excluded from the study.

Age- and sex-matched, hospital-based controls were selected from among the patients, who had acclimatized in high altitude and were admitted to this hospital for ailments other than AMS, HAPO, HACO, and any ocular conditions.

Sample size was calculated assuming standard deviation of 27 μm in both the groups and mean difference of 10 μm with alpha error of 5% and power of 80%, two-sided. The sample size was calculated as 114 cases and 114 controls. We enrolled 124 cases and 126 controls in our study. Power of the study was also calculated a posteriori for hierarchical modeling and was found adequate (85%).

Ocular examination of all study participants was carried out using slit-lamp examination to examine lids, conjunctiva, tear film break-up time, cornea, anterior chamber, pupil, and lens. Fundus was examined with 90 D and indirect ophthalmoscopy. Central corneal thickness (CCT) was measured by ultrasound pachymetry (DGH – 555 B, Pachette 4; DGH Technology, Inc., Exton, PA, USA) after instillation of one drop of 0.5% proparacaine hydrochloride eye drop, on the first day of admission to hospital and was recorded daily till the patient was discharged. The mean of eight readings was taken. SpO2 levels were measured daily at the same time as pachymetry. All cases were given standard therapy recommended for HAPO. Supplemental oxygen at the rate of 3 L/min was instituted till they improved symptomatically or oxygen level improved more than 90% and they had no signs of HAPO. These patient parameters were compared with individuals hospitalized for low back pain, minor surgical procedures, and fractures at 11,400 feet and who had been in high altitude for more than 6 months. The control group was not given any supplemental oxygen.

Vision was checked by near-vision charts at the patients' bedside on arrival to the hospital and before undergoing discharge. Written consent was obtained from all participants included in study. We adhered to the guidelines of the Declaration of Helsinki. The study was approved by local institutional ethical committee.

A database was created in MS Excel. The continuous variables were described with the help of mean and standard deviation. The parameter between HAPO and control group was compared using unpaired t-test, and the parameters before and after oxygen therapy in HAPO and control groups were compared using paired t-test. Correlation was observed using Pearson's correlation. Hierarchical modeling was done to assess the effect of change in CCT in patients with HAPO. Data analysis was done using STATA 13.1 ver I/C. The level of significance was taken as 0.05.


  Results Top


The total number of cases and controls was 124 and 126, respectively. The mean age of controls and cases was 31.2 ± 7.4 and 31.6 ± 7.7 years, respectively. The mean CCT and oxygen level are shown in [Table 1].
Table 1: Description of parameters

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Cases had significantly lower oxygen level at baseline when compared with controls (P < 0.001). However, there was no difference in oxygen levels in the two groups after oxygen had been administered to cases. The oxygen level in the HAPO group improved from 87.8 ± 6.8% at arrival to 95.1 ± 2.6% after treatment. There was no change in visual acuity in patients with HAPO and in controls.

The mean corneal thickness decreased in all cases (right eye 536.3 ± 36 μm on arrival in hospital decreased to 524.6 ± 35.4 μm on the last day of hospitalization. In the left eye, it decreased from 536.6 ± 35.9 μm on arrival in hospital to 524.9 ± 35.1 μm on the last day of hospitalization. In both right and left eyes, pachymetric changes were statistically significant (P < 0.05). The mean corneal thickness of controls was 534 ± 31.5 μm in the right eye and 538.6 ± 48.4 μm in the left eye.

Corneal thickness decreased with improvement in SpO2 level. This decrease occurred in both eyes with improved oxygenation [Figure 1]. The changes correlated with increase with oxygenation (left eye: r = −0.37, P < 0.001; right eye: r = −0.36; P = 0.001). The same is shown in the scatter diagram [Figure 2]. There was no statistically significant change in corneal thickness in controls.
Figure 1: Comparison of before and after reading of pachymetry in two eyes

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Figure 2: Scatter diagram showing relationship between oxygen change (right and left) and change in corneal thickness among high-altitude pulmonary edema cases

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Hierarchical modeling showed a decrease of 1.3 μm in CCT with one unit increase in oxygen mmHg in cases [Table 2].
Table 2: Hierarchical modelling for central corneal thickness (pachymetry)

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  Discussion Top


Our study is the first to compare corneal thickness of cases of HAPO and non-HAPO (controls) and also to study the effects of oxygen supplementation on CCT among patients with HAPO.

Corneal thickness may increase with ascent to higher altitudes. In a study on 40 healthy subjects, the mean CCT of the right eye increased from 540.98 ± 4.34 to 549.73 ± 4.59 μm and from 542.13 ± 6.29 to 547.23 ± 4.59 μm in the left eye, on ascent from 3543 to 9186 feet.[3] This increase was transient, did not affect vision, and decreased to normal on descent to lower altitudes. Vision of healthy lowlanders ascending to high altitude does not alter because the cornea is structurally stable. In our study too, we did not observe any change in vision in HAPO cases and in controls.

In individuals with radial keratotomy, there is preferential expansion in the incised areas of the cornea resulting in peripheral corneal expansion and central corneal flattening causing a hyperopic shift, which adversely affects distant vision.[7] Another study found individuals with laser in situ keratomilieusis developing mild blurring of vision due to occurrence of myopia in extreme high altitude though this did not visually disable them.[8]

Researchers using anterior segment optical coherence tomography found that corneal thickness increased on ascent to high altitude due to an increment in stromal thickness in all cases due to hypoxic decrease in endothelial cell function which is responsible for corneal deturgescence and hypoxic anaerobic metabolism of epithelial cells instead of oxidative metabolism, resulting in increased lactate production in the corneal stroma. This results in osmotic influx of water and stromal hydration. The same authors found that increased CCT was associated with decreased AMS score and improved HR and SpO2 levels.[9] This is in contrast to our study in which we found thicker corneas with decreased SpO2 and corneal thickness decreased with systemic supplemental oxygen. The same effect was seen in another study where a slower route of ascent by one cohort had better acclimatization, improved systemic oxygenation, and decreased incidence of AMS and a more rapid ascent corresponded with greater numbers of AMS.[6] The same authors have stated that though cornea is normally dependent on diffusion of atmospheric oxygen into the tear film, in conditions of low oxygen supply from the environment, the modality of oxygen in aqueous may help in oxygenation of the endothelium. In our study, we found reduction in corneal thickness on supplemental oxygen therapy which possibly was due to the same phenomenon.

Two studies have reported an increase in CCT with altitude exposure and found it to be associated with decreased incidence of AMS.[9],[10] They hypothesized that though increased systemic oxygen level reduces AMS occurrence, it does not reduce corneal stromal thickness. However, our study showed that cornea was thicker in patients with HAPO and simultaneously they had low SpO2 levels. Systemic supplemental oxygen therapy reversed the process by improving the SpO2 levels and decreased corneal thickness by improving aqueous oxygen concentration which possibly had a dominant role in improving endothelial function and decreasing stromal edema.

In our study, both the cases and controls were in the same altitude at the time of the study, so there was no change in the atmospheric pressure or atmospheric oxygen which could have affected the oxygen level of the tear film. Therefore, corneal thickness could not have been changed by atmospheric oxygen. Reduction of corneal thickness in our patients with HAPO, on being given systemic oxygen, was possibly due to increased oxygen diffusion into the aqueous.

Patients suffering from HAPO were stationed in very far-flung and inaccessible areas which had only basic medical facilities provided by a medical assistant who immediately gave oxygen to the patients to prevent death. These medical assistants did not have a pachymeter, nor were they trained to measure the corneal thickness. Therefore, the first place where pachymetry was measured was at 11,400 feet in a multispeciality tertiary care hospital where an ophthalmologist was stationed. The patients, on discharge from hospital, were sent on sick leave and would return to units in low altitude, so could not be followed up for repeat pachymetry.

We had conducted a study in high altitude, comparing the pachymetry of highlanders and lowlanders at 11,400 feet. The results of our study were as follows: a mean CCT of 532.7 μm (34.71 μm) in right eye and 534.4 μm (35.9 μm) in left eye in lowlanders; compared with mean CCT of 520.7 μm (32.5 μm) in right eye and CCT of 521.3 μm (33.8 μm) in left eye of highlanders.[11] In this study too, we found CCT of controls to be 534 ± 31.5 in the right eye and 538.6 ± 48.4 in the left eye. Initial SpO2 of patients was much lower at the onset of illness and CCT could not be measured at that time due to lack of specialized equipment in these areas.

We also attempted to quantify the change in pachymetry with unit increase in oxygen saturation and found that for every unit increase in oxygen level in HAPO cases, a decrease of 1.3 μm was found in pachymetry. However, the findings may need to be corroborated with further studies among patients with HAPO.

There are few limitations in our study. First, the study was restricted to male patients only; hence, generalization of the study is limited. Second, corneal thickness could not be measured at the site of occurrence of HAPO and was only measured when the patient was brought to the hospital. Finally, controls were used only to compare the readings of corneal thickness while they were not given supplemental oxygenation. Our results also show that following oxygen therapy in cases, corneal thickness reduced even though there was no initial difference in baseline pachymetry of cases versus controls.


  Conclusion Top


Our study is the first to compare corneal thickness of cases of HAPO and non-HAPO (controls) and also to study the effects of oxygen supplementation on CCT amongst patients with HAPO. Corneal thickness increases in patients suffering from HAPO though vision is not affected. Treatment with oxygen therapy not only improves their systemic condition but reduces the central corneal thickness. On attempting to quantify the change in pachymetry with unit increase in oxygen saturation we found that for every unit increase in oxygen level in HAPO cases, there was a decrease of 1.3 μm in pachymetry.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Paralikar SJ. High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment. Indian J Occup Environ Med 2012;16:59-62.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Singh I, Roy SB. High altitude pulmonary edema: Clinical, hemodynamic, and pathologic studies. In: Command UA, Ra D, editors. Biomedicine of high terrestrial elevation problems. Washington D.C: 1969. p. 108-20.  Back to cited text no. 2
    
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Jha KN. High altitude and the eye. Asia Pac J Ophthalmol (Phila) 2012;1:166-9.  Back to cited text no. 3
    
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Karakucuk S, Mujdeci M, Baskol G, Arda H, Gumus K, Oner A, et al. Changes in central corneal thickness, intraocular pressure, and oxidation/antioxidation parameters at high altitude. Aviat Space Environ Med 2012;83:1044-8.  Back to cited text no. 4
    
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Kapoor S. High-altitude ophthalmic changes: An often overlooked entity. J Appl Physiol (1985) 2013;115:949.  Back to cited text no. 5
    
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Bosch MM, Barthelmes D, Merz TM, Knecht PB, Truffer F, Bloch KE, et al. New insights into changes in corneal thickness in healthy mountaineers during a very-high-altitude climb to mount Muztagh Ata. Arch Ophthalmol 2010;128:184-9.  Back to cited text no. 6
    
7.
Mader TH, White LJ, Johnson DS, Barth FC. The ascent of Mount Everest following radial keratotomy. Wilderness Environ Med 2002;13:53-4.  Back to cited text no. 7
    
8.
Dimmig JW, Tabin G. The ascent of mount everest following laser in situ keratomileusis. J Refract Surg 2003;19:48-51.  Back to cited text no. 8
    
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Willmann G, Schatz A, Zhour A, Schommer K, Zrenner E, Bartz-Schmidt KU, et al. Impact of acute exposure to high altitude on anterior chamber geometry. Invest Ophthalmol Vis Sci 2013;54:4241-8.  Back to cited text no. 9
    
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Morris DS, Somner JE, Scott KM, McCormick IJ, Aspinall P, Dhillon B, et al. Corneal thickness at high altitude. Cornea 2007;26:308-11.  Back to cited text no. 10
    
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Patyal S, Arora A, Yadav A, Sharma VK. Corneal thickness in highlanders. High Alt Med Biol 2017;18:56-60.  Back to cited text no. 11
    


    Figures

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    Tables

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