Population Prevalence, Pattern and Associated Factors for Retinal Diseases at High Altitude in Nepal.

Background: Retinal diseases are common at high altitudes due to a cascade of changes caused by hypoxia. The aim of this study is to assess the population prevalence, pattern and associated factors of retinal disorders at high altitude in Nepal. Methodology: A cross-sectional study was conducted at three selected high-altitude districts (over 2500 meters) of Nepal. Subjects were at least 40 years old, and the target sample size was 309. A detailed history was taken. Visual acuity, blood sugar, blood pressure, and oxygen saturation were measured. Anterior and posterior ocular evaluations were conducted by retina specialists using slit lamp and indirect ophthalmoscopy. Results: A total of 338 participants were recruited, with nearly equal numbers from the three districts with mean age of 57.0 (S.D 11.1) years. Two-thirds (63.9%) were females; 38.2% were illiterate, and 46.7% were farmers. Average blood oxygen saturation was 87.2% (S.D 4.1%). Systemic hypertension and diabetes mellitus were found in 58% and 11%, respectively. Retinal diseases were found in 176 (52.5%), with bilateral involvement in 157 (46.9%). The major retinal diseases were hypertensive retinopathy (32.2%), high-altitude retinopathy (10.4%), age-related macular degeneration (AMD) (8.1%), branch vein occlusion (BRVO) (2.1%), and diabetic retinopathy (DR) (1.8%). The multivariate analysis showed significant association of retinal diseases with age and hypertension. Best corrected visual acuity better than 6/18 was present in 96.7%. Conclusion: Over half of the study participants had retinal diseases, with hypertensive retinopathy, AMD, and high-altitude retinopathy as the most common retinal problems. A significant association of retinal diseases was found with ageing, and hypertension. Access to eye care services and control of systemic hypertension along with patient education should be emphasized among people living at high-altitude.

AQP4- and Kir4.1-Mediated Müller Cell Oedema Is Involved in Retinal Injury Induced By Hypobaric Hypoxia.

Hypobaric hypoxia is the main cause of high-altitude retinopathy (HAR). Retinal oedema is the key pathological change in HAR. However, its pathological mechanism is not clear. In this study, a 5000-m hypobaric hypoxic environment was simulated. Haematoxylin and eosin (H&E) staining and electrophysiological (ERG) detection were used to observe the morphological and functional changes in the retina of mice under hypobaric hypoxia for 2-72 h. Toluidine blue staining and transmission electron microscopy were used to observe the morphology of Müller cells in the hypobaric hypoxia groups. The functional changes and oedema mechanism of Müller cells were detected by immunofluorescence and western blotting. The expression levels of glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and inwardly rectifying potassium channel subtype 4.1 (Kir4.1) in Müller cells were quantitatively analysed. This study revealed that retinal oedema gradually increased with prolonged exposure to a 5000-m hypobaric hypoxic environment. In addition, the ERG showed that the time delay and amplitude of the a-wave and b-wave decreased. The expression of GS decreased, and the expression of GFAP increased in Müller cells after exposure to hypobaric hypoxia for 4 h. At the same time, retinal AQP4 expression increased, and Kir4.1 expression decreased. The oedema and functional changes in Müller cells are consistent with the time point of retinal oedema. In conclusion, Müller cell oedema is involved in retinal oedema induced by hypobaric hypoxia. An increase in AQP4 and a decrease in Kir4.1 are the main causes of Müller cell oedema caused by hypobaric hypoxia.

High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Retinal Vascular Changes in Response to Hypoxia: A High-Altitude Expedition Study.

Westwood, Jessica, India Mayhook-Walker, Ciaran Simpkins, Andrew Darby-Smith, Dan Morris, and Eduardo Normando. Retinal vascular changes in response to hypoxia: a high-altitude expedition study. High Alt Med Biol. 25:49-59, 2024. Background: Increased tortuosity and engorgement of retinal vasculature are recognized physiological responses to hypoxia. This can lead to high-altitude retinopathy (HAR), but incidence reports are highly variable, and our understanding of the etiological mechanisms remains incomplete. This study quantitatively evaluated retinal vascular changes during an expedition to 4,167 m. Methods: Ten healthy participants summited Mount Toubkal, Morocco. Fundus images were taken predeparture, daily throughout the expedition, and 1 month postreturn. Diameter and tortuosity of four vessels were assessed, in addition to vessel density and features of HAR. Results: Significant (p ≤ 0.05) increases in tortuosity and diameter were observed in several vessels on high-altitude exposure days. There was a strong correlation between altitude and supratemporal retinal artery diameter on days 2, 3, and 6 of the expedition (r = 0.7707, 0.7951, 0.7401, respectively; p < 0.05). There was a significant increase in median vessel density from 6.7% at baseline to 10.0% on summit day. Notably there were no incidences of HAR. Conclusion: Physiological but not pathological changes were seen in this cohort, which gives insight into the state of the cerebral vasculature throughout this expedition. These results are likely attributable to relatively low altitude exposure, a conservative ascent profile, and the cohort's demographic. Future study must include daily retinal images at higher altitudes and take steps to mitigate environmental confounders. This study is relevant to altitude tourists, patients with diabetic retinopathy or retinal vein occlusion, and critically ill patients.

Eye disease and international travel: a critical literature review and practical recommendations.

RATIONALE FOR REVIEW: Eye diseases pose a significant public health and economic burden, particularly for travellers exposed to ocular hazards who may lack access to specialist eye care. This article offers an evidence-based review for travel-health practitioners, with a particular emphasis on ocular infections and trauma that are more prevalent among travellers. Providing an overview of these issues will allow travel health practitioners to comprehensively address ophthalmic considerations of travel. METHODS: A systematic literature search was conducted on PubMed and Embase electronic databases, using keywords related to travel medicine and ophthalmology. Inclusion was based on the relevant contribution to epidemiology, aetiology, diagnostics, management and long-term consequences of travel-related eye conditions. The data were analysed using narrative synthesis. KEY FINDINGS: This literature review highlighted that various travel-related eye conditions may occur. Travellers should be aware of the risk of travel-related ocular complications, which can arise from ocular infections, high-risk activities, high altitude and space travel. The economic and logistical challenges associated with medical tourism for ophthalmic procedures are discussed. For travellers with pre-existing eye conditions or visual impairment, careful planning may be needed to promote eye health and ensure safety of travel. CONCLUSIONS: Travel medicine practitioners should have a comprehensive understanding of the major ocular risks associated with overseas travel, including eye infections, eye injuries and solar eye damage. Further research in this area can enhance overall wellness and alleviate the burden of ocular diseases on travellers. Evidence-based guidelines based on research can also improve the quality of care and prevent long-term vision problems.

Quantify retinal structure in high-altitude residents with and without high altitude polycythemia.

BACKGROUND: To assess retinal structural parameters in high-altitude (HA) residents with and without high altitude polycythemia (HAPC) and to elucidate the relationship between retinal structural parameters and hemoglobin (HGB). METHODS: This cross-sectional study included 55 HAPC patients and 52 healthy HA residents. Retinal structural parameters included retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters and retinal vessel diameter. RNFL thickness were acquired from spectral domain optical coherence tomography (SD-OCT) built-in software. ONH parameters including neuroretina rim height, cup area, disc area and vertical cup/disc ratio were obtained by OCT built-in software and ImageJ software. Retinal vessel measurements including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and AVR (artery/vein ratio) were calculated by revised formulas for summarizing retinal vessel diameters. All parameters were compared between HAPC group versus healthy HA group. The associations between retinal parameters and HGB were assessed by Pearson correlation analyses. RESULTS: In comparison of HAPC group versus healthy HA group, RNFL thickness was thicker in the nasal quadrant of the optic disc in HAPC group (74.82 ± 14.4 VS. 66.06 ± 13.71 µm, P = 0.002). Bigger disc area and bigger cup area were also observed in HAPC group (all P < 0.05). Meanwhile, the value of CRVE was higher in HAPC group which suggested that retinal veins dilated significantly in HAPC patients (P < 0.001), however, CRAE and AVR were comparable between groups. Pearson analyses revealed that HGB was positive correlated with CRVE in HAPC group (r = 0.469, P = 0.003). CONCLUSIONS: long-term HA exposure secondary HAPC could result in thickened RNFL, enlarged ONH and dilated retinal veins. Moreover, increased blood viscosity caused by HGB should be responsible for dilated veins, but not for thickened RNFL and enlarged ONH. This study deepens the understanding of the impact of HA environment on retina.

Integrative analysis of miRNA-mRNA network in high altitude retinopathy by bioinformatics analysis.

High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA-mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA-mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.

Pulmonary embolism, frostbite and high-altitude retinopathy - a combination of life- and sight-threatening vascular complications at high altitude.

The effects of high altitude on the human vascular system are well described. This case demonstrates an interesting combination of vascular complications at high altitude which were both life- and sight-threatening. In May 2017, during an attempt on Mount Everest, a 58-year-old man was forced to descend from 8000 m because of adverse weather. He suffered significant frostbite of his right hand, later requiring termination of the distal phalanx of one of the affected digits. He also experienced increasing breathlessness and went on to develop pleuritic chest pain. A CT pulmonary angiogram performed upon return to sea level revealed multiple small sub-segmental pulmonary emboli. He was anticoagulated for three months and made a full recovery. The patient also reported visual loss in the left eye and on ophthalmic examination was found to have multiple retinal haemorrhages including a left macular haemorrhage, consistent with high altitude retinopathy. The retinal haemorrhages settled with conservative management. The vascular complications suffered by this patient demonstrate the potentially fatal changes that can occur at altitude. They also serve to act as a reminder for physicians, even at sea level of the potential complications in patients returning from high altitude.

Visual outcome of retinal vein occlusion in patients residing at high altitude.

OBJECTIVE: To study visual outcome in patients of high altitude retinopathy presenting with retinal venous occlusion. METHODS: The randomised clinical trial study was conducted at the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, from January 2013 to December 2015, and comprised eyes of lowlanders. Patients staying at high altitude (>8,000 feet above sea level) as part of their service duty and presented with retinal venous occlusive disease were included. Patients with history of diabetes, hypertension, glaucoma, any pre-existing retinal disease or age-related conditions responsible for decreased vision were excluded. Detailed ocular as well as systemic examination was carried out to establish the diagnosis of retinal venous occlusion. Patients were divided into two groups. First group was observed over a period of 6 months and labelled as control group, whereas the second group was treated with intravitrealbevacizumab and labelled as intervention group. Complete ocular examination was carried out in all patients at 4 weeks, 3 months and 6 months. SPSS 21 was used for data analysis. RESULTS: A series of 32 eyes of 28 male patients were included. The overall mean age was 31.40±3.40 years. The mean altitude of their temporary stay was 4,120±941 metres above sea level and the mean duration of stay was 6.80±4.13months. Besides, 21(75%) subjects were smokers. Moreover, 26(81.25%) eyes had central retinal vein occlusion while branch retinal vein occlusion was seen in 6(18.75%) eyes. The mean visual acuity in the control group was 0.70±0.56 on Logarithm of the Minimum Angle of Resolution chart at the presentation while it was 0.26±0.87, 0.20±0.32 and 0.15±0.23 after 4 weeks, 3 months and 6 months, respectively. The mean best corrected visual acuity in intervention group was 0.68 ± 0.46 before treatment and 0.15±0.11, 0.12±0.11 and 0.10±0.08 at 4 weeks, 3 months and 6 months, respectively. Significant post-intervention change was observed in best corrected visual acuity at 6 months (p<0.05) in patients who presented with severe visual loss. CONCLUSIONS: Treatment with intravitrealbevacizumab may be considered in patients with severe visual loss at presentation.

Retinal Hemorrhage in a High-Altitude Aid Post Volunteer Doctor: A Case Report.

Bhandari, Sanjeeb Sudarshan, Pranawa Koirala, Nirajan Regmi, and Sushil Pant. Retinal hemorrhage in a high-altitude aid post volunteer doctor: a case report. High Alt Med Biol. 18: 285-287, 2017.-High-altitude retinal hemorrhages (HARHs) are seen at altitudes more than 3000 m, are usually multiple, flame shaped, and adjacent to blood vessels. Development near the macula causes blurring of vision, otherwise, they are symptomless and self-limiting. They often develop during the first few days after ascent to high altitude and subjects often suffer from acute mountain sickness (AMS) or high-altitude cerebral edema (HACE). People going to high altitude for the first time are more susceptible to retinal hemorrhages than experienced climbers and high-altitude dwellers. We present a case of a 31-year-old male doctor who developed sudden unilateral blurring of vision without any other symptoms after 6 weeks of volunteering at a high-altitude aid post in Nepal. There were no features suggestive of AMS or HACE. All examinations were normal except for fundoscopic examination in the left eye, which determined macular retinal hemorrhage. Although he was reluctant to descend, he was counseled to descend and refrained from further ascent to higher altitude, which could accentuate hypoxemia and any strenuous activities that increase intraocular pressure. He recovered his vision after few weeks in Kathmandu and his retinal hemorrhages regressed. Hypoxia exacerbated by repeated bouts of rapid ascent to further higher altitudes may have contributed to his HARH. This suggests that unilateral retinal hemorrhages can develop even after several weeks at high altitude without concomitant AMS or HACE. People going to high altitude are reluctant to retreat, before reaching their target, when they suffer from HARH. The same is shown by a physician. So it is very important for healthcare professionals working at high altitudes especially in the Himalayas of Nepal to have a good knowledge about HARH and its proper treatment.