Separate and Combined Effects of Hypoxia and Horizontal Bed Rest on Retinal Blood Vessel Diameters

Citation: Louwies T, Jaki Mekjavic P, Cox B, et al. Separate and combined effects of hypoxia and horizontal bed rest on retinal blood vessel diameters. Invest Ophthalmol Vis Sci. 2016;57:4927-4932. DOI:10.1167/ iovs.16-19968 PURPOSE. To assess the separate and combined effects of exposure to prolonged and sustained recumbency (bed rest) and hypoxia on retinal microcirculation. METHODS. Eleven healthy male subjects (mean 6 SD age ¼ 27 6 6 years; body mass index [BMI] ¼ 23.7 6 3.0 kg m À2 ) participated in a repeated-measures crossover design study comprising three 21-day interventions: normoxic bed rest (NBR; partial pressure of inspired O 2 , P i O 2 ¼ 133.1 6 0.3 mm Hg); hypoxic ambulation (HAMB; P i O 2 ¼ 90.0 6 0.4 mm Hg), and hypoxic bed rest (HBR; P i O 2 ¼ 90.0 6 0.4 mm Hg). Central retinal arteriolar (CRAE) and venular (CRVE) equivalents were measured at baseline and at regular intervals during each 21-day intervention. RESULTS. Normoxic bed rest caused a progressive reduction in CRAE, with the change in CRAE relative to baseline being highest on day 15 (DCRAE ¼ À7.5 lm; 95% confidence interval [CI]: À10.8 to À4.2; P < 0.0001). Hypoxic ambulation resulted in a persistent 21-day increase in CRAE, reaching a maximum on day 4 (DCRAE ¼ 9.4 lm; 95% CI: 6.0-12.7; P < 0.0001). During HBR, the increase in CRAE was highest on day 3 (DCRAE ¼ 4.5 lm; 95% CI: 1.2-7.8; P ¼ 0.007), but CRAE returned to baseline levels thereafter. Central retinal venular equivalent decreased during NBR and increased during HAMB and HBR. The reduction in CRVE during NBR was highest on day 1 (DCRVE ¼ À7.9 lm; 95 CI: À13.3 to À2.5), and the maximum DCRVE during HAMB (24.6 lm; 95% CI: 18.9-30.3) and HBR (15.2 lm; 95% CI: 9.8-20.5) was observed on days 10 and 3, respectively. CONCLUSIONS. The diameters of retinal blood vessels exhibited a dynamic response to hypoxia and bed rest, such that retinal vasodilation was smaller during combined bed rest and hypoxia than during hypoxic exposure

Hypercapnia augments resistive exercise‐induced elevations in intraocular pressure in older individuals

The present study assessed the effect of 6° head down (establishing the cephalad displacement noted in astronauts in microgravity) prone (simulating the effect on the eye) tilt during rest and exercise (simulating exercise performed by astronauts to mitigate the sarcopenia induced by unloading of weight‐bearing limbs), in normocapnic and hypercapnic conditions (the latter simulating conditions on the International Space Station) on IOP.Volunteers (average age = 57.8 ± 6 yrs.; N = 10) participated in two experimental sessions, each comprising: i) 10‐min rest, ii) 3‐min handgrip dynamometry (30% max), and iii) 2‐min recovery, inspiring either room air (NCAP), or a hypercapnic mixture (1% CO2, HCAP). We measured IOP in the right eye, cardiac output (CO), stroke volume (SV), heart rate (HR) and mean arterial pressure (MAP) at regular intervals. Baseline IOP in the upright seated position while breathing room air was 14.1 ± 2.9 mmHg. Prone 6° HDT significantly (p < 0.01) elevated IOP in all three phases of the NCAP (rest: 27.9 ± 3.7 mmHg; exercise: 32.3 ± 4.9 mmHg; recovery: 29.1 ± 5.8 mmHg) and HCAP (rest: 27.3 ± 4.3 mmHg; exercise: 34.2 ± 6.0 mmHg; recovery: 29.1) trials, with hypercapnia augmenting the exercise‐induced elevation in IOP (p < 0.01). CO, SV, HR and MAP were significantly increased during handgrip dynamometry, but there was no effect of hypercapnia. The observed IOP measured during prone 6°HDT in all phases of the NCAP and HCAP trials exceeded the threshold pressure defining ocular hypertension. The exercise‐induced increase in IOP is exacerbated by hypercapnia

Outcome of 5-Year Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Using “Treat and Extend” Regimen

ObjectiveThe aim of this study is twofold. First, to evaluate the long-term outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in a clinical setting using the “treat-and-extend regimen” (TER) in patients with neovascular age-related macular degeneration (nAMD). Second, to determine the proportion of patients treated with anti-VEGF with good visual acuity (VA), i.e., vision sufficient to maintain a high level of independence.DesignWe conducted a single center retrospective review of patients with treatment-naive nAMD who were treated with anti-VEGF. Patients were treated with anti-VEGF intravitreal injections according to the TER. Patients started treatment with monthly injections of either bevacizumab (1.25 mg/0.05 mL) or ranibizumab (0.5 mg/0.05 mL) until there were no signs present of choroidal neovascularization (CNV) activity. CNV activity was determined from fundus examination and SD-OCT imaging. Follow-up administration of intravitreal injections was extended by 2-week intervals, up to a total of 14 weeks, provided no signs of CNV activity were detected. In some patients, the first treatment was replaced with aflibercept (2 mg/0.05 mL).ParticipantsOn the basis of the inclusion criterion for the study, that patients had to be treated for 5 years, a total of 101 patients were included in the study. In all patients, one eye was treated for a 5-year period, and thus we studied 101 eyes.MeasurementsBest corrected VA was analyzed at baseline and each year during the 5-year follow-up.ResultsVA improved initially after year 1 of the treatment. VA decreased in the subsequent 4 years of treatment, but remained significantly higher from year 1 to year 3 of the treatment compared to baseline values. Patients with good VA followed a similar trend: the proportion increased in the first year, and thereafter gradually decreased during the course of the 5-year follow up. At year 5, the number of patients with good VA decreased to baseline values.ConclusionTER with anti-VEGF for nAMD treatment prevents long-term severe visual loss in real-world setting and maintains patients’ VA at levels sufficient to ensure independence

Ocular changes in metastatic melanoma patients treated with MEK inhibitor cobimetinib and BRAF inhibitor vemurafenib

Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combination with vemurafenib