A recent study published in EBioMedicine provides new insights into the impact of acute elevations of intraocular pressure (IOP) that occur during the disease Glaucoma. This work, in collaboration with Dr. Xinghuai Sun’s group at the Eye and ENT Hospital of Fudan University, was performed at Dr. Wei Wang’s Lab at the Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Science, and Shanghai Center for Brain and Brain-Inspired Intelligence Technology.

Glaucoma is the leading cause of irreversible blindness. Raised IOP is an established risk factor associated with the development and progression of glaucoma. Chronically high IOP causes atrophy of the optic disc (otherwise known as the optic nerve head, the point of exit for nerve fibres travelling from the eye to the brain) and this eventually leads to visual field defects. Acute angle-closure glaucoma (PACG) constitutes an ophthalmic emergency, as it can cause extremely sharp IOP elevation (70 mmHg and above). It is estimated that the worldwide incidence of PACG in people aged 40-80 was 20.17 million in 2013, and this is predicted to rise to 23.36 million in 2020 and 32.04 million in 2040. Asia accounts for about 77% of worldwide PACG cases. Clinical studies of chronic glaucoma have found that visual acuity, which is finest within the central visual field, is relatively preserved until the later stages of the disease. Comparable clinical studies of acute glaucoma, however, are impaired by the high incidence of optical complications such as corneal edema and cataract. This makes it difficult to establish the exact relationship between acute IOP and visual acuity in these patients.

While vision initiates at the retina, it is within the cerebral cortex that seeing ultimately occurs. This study used the best experimental model of human vision (non-human old-world primates) to address this important clinical question by examining activity in the visual cortex while reversibly elevating acute IOP (Figure1). It used an optical method to image cortical activity through a large window onto the brain surface while presenting fine gratings to stimulate the visual pathways.

Figure 1. Experimental protocol. (a) Schematic diagram of the experimental setup. (b) The timeline of IOP elevation in each experiment. The dotted lines indicate various IOP levels (30, 50, 70, and 90 mmHg) for experiments. (c) The region of interest (ROI) and the definition of V1 and V2 border. LS, lunate sulcus; A, anterior; L, lateral. Scale bar, 1 mm. (d) The cortical activity of preferential orientation responses before, during and after IOP elevated to 70 mmHg, respectively. N = 11 hemispheres. n.s. represents P > 0.05. **P < 0.01 compared with pre or post. Error bar denotes SEM.

This study found that acute IOP elevation impaired the ability of the visual cortex to register fine detail, an effect that was progressively more severe toward central visual field (Fig 2). These results show that impairment of fine visual discrimination within the central visual field is the principal consequence of sharp IOP elevation in macaque monkeys, implicating relatively greater dysfunction of a subset of smaller retinal output cells, known to give rise to the so-called ‘parvocellular’ pathway. This study in non-human primates identifies the consequent cortical deficits indicative of visual acuity loss in acute glaucoma patients. In contrast to previous studies of chronic glaucoma, this impairment of central visual acuity implies selective impairment of the parvocellular pathway, in distinction to chronic glaucoma in which this pathway appears to be more resilient.

Figure 2. Cortical responses at different retinal eccentricities during acute IOP elevation. (a) The left panel shows a retinal eccentricity map of the cortical surface in V1 and V2, using false-color to indicate distance from central-most vision. The right panel shows cortical response activity at an SF of 2 cycles/° with superimposed iso-eccentricity contours. Scale bar, 1 mm. (b) Parametric relationship between the cortical response ratios and eccentricity for each SF during 70 mmHg IOP. (c) Statistics of the cortical response ratios (70 mmHg IOP: control) between larger eccentricity (6 – 9°) and smaller eccentricity (4 – 6°) zones in V1, at each SF tested. **P < 0.01, *P < 0.05. N = nine hemispheres. Error bar denotes SEM

These findings have been published as a research article entitled “Impact of Acute Intraocular Pressure Elevation on the Visual Acuity of Non-human Primates”, with Dr. Mengwei Li and Dr. Nini Yuan from the Eye and ENT Hospital of Fudan University as the equal contributing first authors, published online in EBioMedicine June 08, 2019. Dr. Xinghuai Sun and Dr. Wei Wang are the corresponding authors. This research was supported by the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX05 to W.W), the National Natural Science Foundation of China (No. 81430007, No.81790641, and No. 31600846), the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDB32060200 to W.W), the Shanghai Committee of Science and Technology (No.17410712500) and the top priority of clinical medicine center of Shanghai (No.2017ZZ01020).