IOP telemetry in the nonhuman primate
Introduction
Glaucoma is primarily a disease of aging (Gordon et al., 2002, Leske et al., 2003a, Leske et al., 2003b) and is one of the leading causes of blindness in the developed world (Quigley and Broman, 2006). Lowering IOP is the only clinical treatment that has been shown to retard the onset and progression of glaucoma, but once damaged, the optic nerve head (ONH) is thought to be more susceptible to further glaucomatous progression even after clinical intervention has lowered mean IOP to ‘normal’ levels. IOP is a mechanical load, and ONH and scleral biomechanics are also thought to be centrally involved in glaucoma susceptibility, as well as disease onset and progression (Fig. 1) (Zeimer and Ogura, 1989, Burgoyne et al., 2005, Downs et al., 2008, Sigal and Ethier, 2009, Sigal et al., 2010). In this review, we discuss the existing data and ongoing efforts to measure continuous IOP in nonhuman primates (NHP) and humans, and the strengths, weaknesses and general pitfalls of the various approaches used. We review continuous IOP data gathered using telemetry systems, presented in the framework that IOP fluctuations at various timescales may be involved in glaucoma pathogenesis. We also discuss how the dynamic nature of IOP is likely to change with age, racial heritage, and disease in the context of glaucoma susceptibility and progression.
Section snippets
The difference between high frequency and low frequency IOP fluctuations
There is a large and controversial literature surrounding the importance of low frequency fluctuations of clinically measured mean IOP in glaucoma (Sacca et al., 1998, Bengtsson and Heijl, 2005, Bengtsson et al., 2007, Medeiros et al., 2008). These studies all rely on snapshot measurements of IOP that report a mean baseline value at each time point, and those measurements are taken at relatively infrequent intervals (hourly at the most frequent). Recently however, there has been some interest
What is the true IOP in a patient?
IOP is an important risk factor for glaucoma and lowering IOP, even when IOP is in the normal range as defined epidemiologically, remains the only proven-effective treatment for the disease. However, our knowledge of the true character of IOP in humans or how it affects ocular tissues is limited in part by the lack of a continuous IOP monitoring technology for patients. Two telemetry devices have been extensively tested in humans, the first of which is based on a stretch-sensitive contact lens
The relationship of age, racial heritage, and existing disease to the onset and progression of glaucoma
The results of several randomized prospective trials have identified risk factors associated with the development or progression of glaucoma (AGIS, 2000; Gordon et al., 2002, Leske et al., 2003a, Leske et al., 2003b, Miglior et al., 2007). Across these studies, IOP, age, central corneal thickness, increased optic disc cupping, and African ancestry were independently associated with glaucomatous progression. Importantly, age and race (OHTS; univariate only) are the only risk factors other than
The Nycthemeral rhythm and repeatability of IOP patterns
While mean IOP has been shown to have a nycthemeral rhythm in patients (Liu et al., 1998, Liu et al., 1999), clinical studies have shown that this pattern varies between individuals and is not robustly repeatable from day-to-day in the same patient (Realini et al., 2006, Realini et al., 2010, Realini et al., 2011). While the nocturnal rise in IOP has been attributed to habitual supine sleeping position (Jorge et al., 2010), there is some evidence that the nocturnal rise is IOP is still
IOP telemetry in NHPs
To our knowledge, only one system has been successfully used to measure IOP continuously over extended periods in NHPs. This system was developed from fully implantable radiotelemetry systems that have been used to monitor physiologic pressures continuously in large animals (Fig. 6). The benefits of the telemetry system from Konigsberg Instruments, Inc. (Pasadena, CA) are that it allows continuous monitoring of IOP at a 500 Hz measurement frequency for ∼24 months, the pressure sensors have low
The importance of pressure transducer placement
Many commercial pressure telemetry systems use a fluid-filled, gel-tip catheter to transduce the pressure at the catheter tip to a remote pressure transducer included in the electronics/battery package. This system has been used in several studies in rabbits to characterize IOP in response to pharmacological agents (McLaren et al., 1996, McLaren et al., 1999). The electronics/batter/transducer package is too large to be placed subcutaneously in the head however, and is generally placed under
A look ahead to IOP, ocular perfusion pressure (OPP) and intracranial/cerebrospinal pressure telemetry systems on the horizon
Several systems in development hold promise for monitoring the physiologic pressures relevant to glaucoma: IOP, OPP, and cerebrospinal fluid measurement. We have enhanced our unilateral NHP telemetry system (Downs et al., 2011) to measure continuous bilateral IOP, bilateral electro-oculogram, and aortic blood pressure (Fig. 7). Using this enhanced system, OPP is calculated 500 times per second as: central retinal artery blood pressure – IOP. The central retinal artery systolic and diastolic
Clinical implications
Whether it is mean IOP and/or IOP fluctuations that drive glaucomatous pathogenesis, there is a wide spectrum of individual susceptibility to IOP-related glaucomatous vision loss. However, the biomechanical effects of both mean IOP and IOP fluctuations are likely to play a central role in the development and progression of the disease at all IOP levels. There are currently no science-based tools to predict at what level of IOP an individual ONH will be damaged. Eventually, knowing the
Acknowledgments
The author would like to acknowledge Drs. Claude F. Burgoyne and Christopher A. Girkin, whose assistance and clinical and surgical expertise in glaucoma was critical in developing our unilateral and bilateral IOP telemetry system for NHPs.
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2020, Progress in Retinal and Eye ResearchCitation Excerpt :This modeling approach has led to the insight that reduced structural viscoelasticity due to aging or disease may compromise the ability of ocular tissues to maintain perfusion upon sudden changes in IOP. Sudden changes in IOP are physiological and they occur every time we blink or rub our eyes, as confirmed via IOP telemetry in non-human primates (Downs, 2015). Thus, the model led to the formulation of the hypothesis that even physiological changes in IOP might induce pathological changes in the hemodynamics of the optic nerve head if the viscoelasticity provided by the collagen fibers is not intact (Verri et al., 2018; Bociu et al., 2019).