Retinal microvasculature is a potential biomarker for acute mountain sickness

Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema,which is the leading hypothesis of acute mountain sickness(AMS).However,studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature.This study aimed to investigate ocular microcirculation alterations,the only visualized capillaries in the central neural system(CNS),during early-stage AMS using a hypobaric chamber.This study found that after high altitude simulation,the optic nerve showed retinal nerve fiber layer thickening(P=0.004–0.018)in some locations,and the area of the optic nerve subarachnoid space(P=0.004)enlarged.Optical coherence tomography angiography(OCTA)showed increased retinal radial peripapillary capillary(RPC)flow density(P=0.003–0.046),particularly on the nasal side of the nerve.The AMSpositive group had the largest increases in RPC flow density in the nasal sector(AMS-positive,?3.21±2.37;AMS-negative,?0.01±2.16,P=0.004).Among multiple ocular changes,OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms(beta=0.222,95%CI,0.009–0.435,P=0.042).The area under the receiver operating characteristics curve(AUC)for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882(95%CI,0.746–0.998).The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS.RPC OCTA endpoints may serve as a rapid,noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes.

Pressure balance and imbalance in the optic nerve chamber： The Beijing Intracranial and Intraocular Pressure (iCOP) Study

To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

Finite element analysis of trans-lamina cribrosa pressure difference on optic nerve head biomechanics: the Beijing Intracranial and Intraocular Pressure Study

The present study aims to assess the potential difference of biomechanical response of the optic nerve head to the same level of trans-lamina cribrosa pressure difference(TLCPD) induced by a reduced cerebrospinal fluid pressure(CSFP) or an elevated intraocular pressure(IOP). A finite element model of optic nerve head tissue(pre-and post-laminar neural tissue, lamina cribrosa, sclera, and pia mater) was constructed. Computed stresses, deformations, and strains were compared at each TLCPD step caused by reduced CSFP or elevated IOP. The results showed that elevating TLCPD increased the strain in optic nerve head,with the largest strains occurring in the neural tissue around the sclera ring. Relative to a baseline TLCPD of 10 mmHg, at a same TLCPD of 18 mmHg, the pre-laminar neural tissue experienced 11.10% first principal strain by reduced CSFP and 13.66% by elevated IOP, respectively. The corresponding values for lamina cribrosa were 6.09% and 6.91%. In conclusion, TLCPD has a significant biomechanical impact on optic nerve head tissue and, more prominently, within the pre-laminar neural tissue and lamina cribrosa. Comparatively, reducing CSFP showed smaller strain than elevating IOP even at a same level of TLCPD on ONH tissue, indicating a different potential role of low CSFP in the pathogenesis of glaucoma.

Long-term follow-up of optic neuropathy in chronic low cerebrospinal fluid pressure monkeys: the Beijing Intracranial and Intraocular Pressure(iCOP) Study

Dear Editor,Clinical and anatomic investigations strongly suggest that a low orbital cerebrospinal fluid pressure (CSFP), parallel to an elevated intraocular pressure (IOP), may have a role in the pathogenesis of optic neuropathy (Ren et al., 2011, Wang et al., 2012). Optic neuropathy including glaucoma demonstrated structural alterations in the optic nerve head (ONH)and retinal nerve fiber layer (RNFL), as well as functional abnormalities such as visual field (VF) that eventually cause severe visual impairment and blindness.