Normal Intraocular Pressure Levels Research Articles

Glial cells as a promising therapeutic target of glaucoma: beyond the IOP.

Glial cells, a type of non-neuronal cell found in the central nervous system (CNS), play a critical role in maintaining homeostasis and regulating CNS functions. Recent advancements in technology have paved the way for new therapeutic strategies in the fight against glaucoma. While intraocular pressure (IOP) is the most well-known modifiable risk factor, a significant number of glaucoma patients have normal IOP levels. Because glaucoma is a complex, multifactorial disease influenced by various factors that contribute to its onset and progression, it is imperative that we consider factors beyond IOP to effectively prevent or slow down the disease's advancement. In the realm of CNS neurodegenerative diseases, glial cells have emerged as key players due to their pivotal roles in initiating and hastening disease progression. The inhibition of dysregulated glial function holds the potential to protect neurons and restore brain function. Consequently, glial cells represent an enticing therapeutic candidate for glaucoma, even though the majority of glaucoma research has historically concentrated solely on retinal ganglion cells (RGCs). In addition to the neuroprotection of RGCs, the proper regulation of glial cell function can also facilitate structural and functional recovery in the retina. In this review, we offer an overview of recent advancements in understanding the non-cell-autonomous mechanisms underlying the pathogenesis of glaucoma. Furthermore, state-of-the-art technologies have opened up possibilities for regenerating the optic nerve, which was previously believed to be incapable of regeneration. We will also delve into the potential roles of glial cells in the regeneration of the optic nerve and the restoration of visual function.

Management of Primary Open Angle Glaucoma (POAG): Ayurvedic and Modern Approaches

Primary open-angle glaucoma (POAG) is a chronic disease characterized by elevated intraocular pressure (IOP), optic nerve damage, and visual field loss. This review explores the management of glaucoma from both Ayurvedic and modern medical perspectives, discussing their similarities, differences, and potential benefits. Modern therapeutic approaches include medication, laser therapy, and surgery to lower IOP and prevent visual field damage. However, glaucoma progression and optic nerve damage can occur even with normal IOP levels. Ayurveda views POAG as a manifestation of Adhimantha, primarily involving Pitta and Rakta doshas. Ayurvedic treatments focus on improving ocular health through various therapies, herbal formulations, and lifestyle modifications. Integrating Ayurvedic and modern approaches may provide a comprehensive approach to glaucoma management, enhancing patient outcomes.

Синдром «голубых склер» и его сочетание с глаукомой (обзор литературы и клиническое наблюдение)

This paper reviews the key risk factors and clinical manifestations of blue sclerae, which include a large group of diseases of various origins. Generally, this syndrome is genetically determined and is a constant phenotypic sign of osteogenesis imperfecta. In addition to the classic triad of blue sclera, brittle bones, and hearing loss, many authors refer glaucoma to as an ocular manifestation of brittle bone disease in addition to thin cornea and low corneoscleral rigidity. The combination of osteogenesis imperfecta type 1 and primary open-angle glaucoma is a novel phenotypic association. The most effective way of controlling intraocular pressure (IOP) in this condition is surgical intervention. Case report of a combination of glaucoma and syndromic connective tissue disease that appeared 15 years after the first visit to an ophthalmologist for recurrent ocular hypertension is presented. Selective laser trabeculoplasty and a fixed-dose combination of 0.3% bimatoprost and 0.5% timolol provided normal IOP levels. Ultrathin corneas and systemic hypotension do not rule out the need for further surgery. KEYWORDS: blue sclera, glaucoma, osteogenesis imperfecta, corneal thickness. FOR CITATION: Beletskaya T.A., Kozina E.V., Dmitrenko D.V., Gavrilova Yu.I. Blue sclerae and their association with glaucoma (a review and case report). Russian Journal of Clinical Ophthalmology. 2023;23(4):225–230 (in Russ.). DOI: 10.32364/2311-7729-2023-23-4-9.

Изменение клеток Лангерганса и структуры нервных волокон роговицы у пациентов с глаукомой по данным лазерной конфокальной микроскопии

The most important tasks of preventing blindness and low vision in primary open-angle glaucoma (POAG) are its early diagnosis and quality monitoring in order to stabilize the glaucoma process. Purpose. To analyze the state of Langerhans inflammatory cells and the structure of corneal nerve fibers in patients with POAG. Material and methods. The study included 46 patients. The main group - 26 patients (52 eyes) aged 39 to 80 years - diagnosed with POAG stages I-IV. Control group - 20 patients (40 eyes) - ophthalmologically healthy volunteers with a normal level of intraocular pressure (IOP) and no signs of POAG at the age from 36 to 72 years. Patients underwent: visometry, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, gonioscopy, contour tonometry using the Pascal method, optical coherence tomography (OCT) of the optic nerve discs (Zeiss Stratus 3000) and confocal microscopy of the cornea (CMR) (HRT III, Rostock Cornea Module). Results. In patients with POAG, according to CMR data, structural changes were revealed in the layer of nerve fibers of the cornea, and abnormalities in the structure and number of inflammatory macrophages (Langerhans cells) were also identified. The interocular asymmetry of CNF was investigated in patients with different stages of glaucoma in paired eyes. Conclusion. Аnalyzing the structure of corneal nerve fibers and Langerhans cells can be used as a diagnostic algorithm in patients with POAG. Key words: glaucoma, confocal microscopy, corneal nerve fibers, Langerhans cells, optical coherence tomography.

Relationship between Corneal Morphogeometrical Properties and Biomechanical Parameters Derived from Dynamic Bidirectional Air Applanation Measurement Procedure in Keratoconus.

The morphogeometric analysis of the corneal structure has become a clinically relevant diagnostic procedure in keratoconus (KC) as well as the in vivo evaluation of the corneal biomechanical properties. However, the relationship between these two types of metrics is still not well understood. The current study investigated the relationship of corneal morphogeometry and volume with two biomechanical parameters: corneal hysteresis (CH) and corneal resistance factor (CRF), both provided by an Ocular Response Analyzer (Reichert). It included 109 eyes from 109 patients (aged between 18 and 69 years) with a diagnosis of keratoconus (KC) who underwent a complete eye examination including a comprehensive corneal topographic analysis with the Sirius system (CSO). With the topographic information obtained, a morphogeometric and volumetric analysis was performed, defining different variables of clinical use. CH and CRF were found to be correlated with these variables, but this correlation was highly influenced by corneal thickness. This suggests that the mechanical properties of KC cornea contribute only in a partial and limited manner to these biomechanical parameters, being mostly influenced by morphogeometry under normal intraocular pressure levels. This would explain the limitation of CH and CRF as diagnostic tools for the detection of incipient cases of KC.

Pathogenic roles of retinal glia in glaucoma

Glaucoma, progressive optic neuropathy, is the first cause of blindness in Japan. Blindness in this disease is induced by damages or degeneration of retinal ganglion cells (RGCs), retinal neurons transmit visual information to brain. An elevated intraocular pressure (IOP) is widely recognized as one of the most important risk factors and that IOP directly damages RGCs by mechanical stress, however, accumulating evidences have shown that a majority of Japanese patients for primary open angle glaucoma shows normal level of IOP. Thus, new target for glaucoma pathology is emerged. In this issue, we introduce potential roles of glial cells for pathogenesis of glaucoma. In the CNS, reactive gliosis has been recognized in a variety of neurodegenerative diseases. Such glial activation is also found in retinae of human glaucoma patients and animal models. Importantly, glial activation precedes RGS degeneration, indicating the possibility that reactive glial cells actively contribute to pathogenesis of glaucoma. In this issue, we will focus on macroglial cells such as Muller cells and astrocytes, and discuss their roles in glaucoma.

Species Differences in the Nutrition of Retinal Ganglion Cells among Mammals Frequently Used as Animal Models.

The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, a retinal nutrition type, and a mixture of both types. 2. Low oxygen concentration levels in the inner retina force the diffusion of oxygen especially in the choroidal nutrition type. Other nutrients might be supplied by surrounding cells, mainly Müller cells. 3. Diffusion in the eye is influenced by the intraocular pressure, which is vital for the retinal ganglion cells but might also influence their proper function. Again, the nutrition types established might explain the differences in normal intraocular pressure levels among different species. 4. Temperature is a critical feature in the eye which has to be buffered to avoid neuronal damage. The most effective buffer system is the increased blood turnover in the choroid which has to be established in all species.

Effect of Hydrogen Sulfide Donor on Intraocular Pressure in Rats

We studied the effect of 1% sodium hydrosulfide solution (NaHS) on intraocular pressure (IOP) in intact rats and those with simulated ocular hypertension induced by prolonged systemic administration of adrenaline. A single administration of hydrogen sulfide donor as drops into the eye cavity caused the hypotensive effect, which was rather weak in the eyes of intact rats and pronounced in those with ocular hypertension. Long-term administration of NaHS by the scheme, against the background of applying adrenaline as inductor, to a large extent, prevented the IOP rise. It has been concluded that hydrogen sulfide is involved in the regulation of intraocular hydrodynamics and maintaining normal IOP levels.

Primary Open-Angle Glaucoma in a Population Associated with High Prevalence of Primary Angle-Closure Glaucoma: The Kumejima Study

To evaluate the prevalence of and risk factors for primary open-angle glaucoma (POAG) in a rural population of southwestern Japan. Population-based cross-sectional study. All residents 40 years of age and older in Kumejima, Okinawa, Japan. Of the eligible 4632 residents 40 years of age and older, 3762 subjects (participant rate, 81.2%) underwent screening examinations, including visual acuity (VA) measurement, slit-lamp examination, Goldmann applanation tonometry, gonioscopy, undilated stereoscopic fundus photographs, autorefractometry, noncontact specular microscopy, pachymetry, and visual field (VF) testing using frequency-doubling technology. If glaucoma or other related ocular disorders were suspected, subjects were referred for definitive examinations including VF testing with the Humphrey Field Analyzer. The diagnosis of POAG was based on the criteria of the International Society for Geographical and Epidemiological Ophthalmology. Prevalence and risk factors of POAG. The prevalence of POAG was 4.0% (95% confidence interval [CI], 3.4%-4.7%); 82% of patients had an intraocular pressure (IOP) less than 22 mmHg, resulting in a prevalence of 3.3% (95% CI, 2.8%-3.9%). Because of POAG, 3 subjects had a VA worse than 20/400 in only 1 eye, and 1 subject had VA loss of worse than 20/400 bilaterally. The average IOP values (mean ± standard deviation) were 14.9 ± 3.2 and 14.6 ± 3.3 mmHg in the right and left eyes, respectively; the IOP values were higher in patients with POAG (15.4 ± 3.3 and 15.2 ± 3.3 mmHg, respectively) than in subjects without glaucoma (14.8 ± 3.1 and 14.4 ± 3.1 mmHg, respectively; P<0.045, Student t test). Multivariate analysis showed that male gender (P = 0.003), older age (P<0.001), higher IOP (P<0.001), longer axial length (P<0.001), and thinner central cornea (P = 0.006) were associated with POAG. High prevalence rates of POAG (4.0%) and POAG with normal IOP levels (3.3%), which were comparable with those on the Japanese mainland, were found in a southwestern rural island of Japan, where the prevalence of primary angle-closure glaucoma (previously reported as 2.2%) was considerably higher than on the Japanese mainland (0.6% in the Tajimi Study) or other countries. The risk factors for POAG included male gender, older age, higher IOP, myopia, and a thinner cornea.

Intraocular pressure in postmenopausal Nigerian women with and without systemic hypertension

Background: Mean intraocular pressure (IOP) in postmenopausal women has been reported higher than that in menstruating women. Also, intraocular pressure is said to be positively correlated with systemic blood pressure. No previous study in Nigeria has compared intraocular pressure in postmenopausal women with and without systemic hypertension. Purpose: To investigate the effects of menopause on intraocular pressure in subjects with and without high blood pressure. Methods: Normotensive and hypertensive premenopausal and postmenopausal subjects in the same agerange of 45 to 55 years were studied. Intraocular pressure was measured with the hand-held Kowa applanation tonometer. Blood pressure was taken in the sitting position at the right upper arm using a manual mercury sphygmomanometer with the right cuff size. The average of two readings was recorded. Results: Mean IOP for premenopausal normotensive women was 14.58 ± 2.56 mmHg whilethat of postmenopausal normotensive women was16.15 ± 1.80 mmHg (p&lt;0.05). Also, the difference in mean IOP between premenopausal hypertensive (16.58 ± 3.23 mmHg) and postmenopausal hypertensive women (18.24 ± 3.89 mmHg)was statistically significant (p&lt;0.05). A statistically significant and positive correlation was observed between IOP and systemic blood pressure in postmenopausal hypertensive women, p&lt;0.05.Conclusion: Menopause significantly increases intraocular pressure. Mean intraocular pressure of hypertensive postmenopausal women was significantly higher than that of normotensive post-menopausal women, (p&lt;0.05). Knowledge of the normal level of intraocular pressure during various stages of the female reproductive cycle may help during glaucoma screening. (S Afr Optom 2011 70(3) 117-122)

Mitigation of the IOP elevation associated with non‐supine sleep positions

AbstractPurpose When a person sleeps in a non‐supine position, the load path through which the weight of the head is transferred to a supporting surface (a pillow, the mattress, an arm, etc.) generally includes one eye. This research quantifies the forces that act on the eye and the potential for extended periods of intraocular pressure (IOP) elevation when the eye is a load bearing element in the "head‐to‐bed" load path.Methods An engineering model of the load path is used to quantify nominal loads on the eye when in side‐ and face‐down sleep positions. The eye is modeled as a fluid filled, thin walled pressure vessel and is included as a load‐bearing structural element in the head‐to‐bed load path. The model is used to simulate a device that provides as alternative load path to mitigate sleep position related elevation of IOP.Results Predictions from a lumped parameter model indicate that individuals who sleep in non‐supine positions will experience elevation of IOP of 3‐5 mmHg. A more sophisticated eye model is used to incorporate deformation of the eye and to show the lumped parameter model estimates of IOP elevation are conservative. This result is supported by a recently published experimental study of measured IOP elevation in dogs during eye manipulation [Keing et al., 2011] which suggests that relatively modest deformations of the eye can nearly double measured IOP levels. A non‐invasive method for alleviation of the external forces that act on the eye during non‐supine sleep is described as a means for altering this load path.Conclusion These results suggest that patients with normal IOP levels during the day may experience significant elevation of IOP levels due to sleeping in non‐supine positions. An approach to mitigate this mechanism of IOP elevation is presented.

血液透析と眼圧

Hemodialysis, a useful treatment for patients with severely compromised renal function, has also unfavorable side effects. In the ophthalmologic area, a rise in intraocular pressure (IOP) during dialysis accompanied by ocular pain has been reported. In our study when measuring IOP, as well as serum osmolality and plasma CO2 pressure every 30 minutes during routine hemodialysis in renal failure patients with a normal aqueous outflow facility, the mean percent changes of IOP to the initial value showed no significant difference at any time, although the changes in serum osmolality decreased significantly. The mean percent changes of plasma CO2 pressure also did not show any significant difference during dialysis. In patients with a poor aqueous outflow facility, the mean percent changes of IOP increased significantly after 90 minutes, with the exception of the change at 180 minutes. The mean percent changes of serum osmolality decreased significantly after starting dialysis. A negative correlation in the mean percent change of IOP with that of serum osmolality was detected. The administration of an intravenous hyperosmotic agent prevented significant changes not only in serum osmolality but also in IOP. Therefore, it is considered that hemodialysis causes a decrease in serum osmolality, resulting in an osmotic gradient between the plasma and the intraocular fluids due to the presence of the blood-ocular barrier. Although the osmotic gradient draws water from the plasma into the eye, if there is no abnormal obstruction in the aqueous outflow pathway, an amount of aqueous humor matching the increase in intraocular fluid goes through the pathway out of the eye to maintain the normal level of IOP. In eyes with an obstructed aqueous outflow pathway, however, this compensatory mechanism of aqueous humor drainage does not work well, and results in an IOP elevation.

Intraocular pressure trends in pregnancy and in the third trimester hypertensive patients.

Systemic blood pressure is positively related to intraocular pressure. During the third trimester of pregnancy decreased intraocular pressure while increased blood pressure has been reported. After taking into account all those factors that can affect intraocular pressure, the present study investigated whether or not the high blood pressure found in late pregnancy influences the known ocular hypotensive effect of late pregnancy. Normotensive subjects in all trimesters of pregnancy and non-pregnant control groups along with third trimester hypertensive subjects were studied. Intraocular pressure was measured with the Goldmann applanation tonometer. In the second and third trimester subjects, the mean intraocular pressure was significantly lower than in the non-pregnant control group. The differences between first and second, first and third, and second and third trimesters of pregnancy were (mean +/- s.d.) -0.5 +/- 1.2 (p < 0.05), -1.5 +/- 1.7 (p < 0.001), and -1.0 +/- 2.1 (p < 0.01) mmHg respectively. The mean difference between third trimester hypertensive and third trimester normotensive pregnant women was 0.53 +/- 1.5 mmHg (p < 0.05). With advancing pregnancy, intraocular pressure decreases. The mean intraocular pressures of third trimester hypertensive pregnant women were significantly higher from that of third trimester non-hypertensives. Knowledge of the normal level of intraocular pressure in various stages of pregnancy may help glaucoma screeners.

Previous Ocular Compression Increases Intraocular Penetration of Systemic Drugs

Intraocular drug penetration is dependent upon the physical and chemical characteristics of the drug, the manner of drug administration and the drug's ability to pass through the blood/aqueous barrier. Most systemically administered drugs do not achieve intraocular therapeutic levels. The authors present a new method to increase the intraocular concentration of intravenously administered drugs based on the premise that ocular hypotony by ocular compression produces a temporary break in the blood/aqueous barrier during the period of hypersecretion that follows to regain normal intraocular pressure levels. Vancomycin introduced parenterally was used as the drug model. The right eye of 22 rabbits served as experimental eye, while the left eye served as control. The concentrations of vancomycin in the aqueous humor half an hour after intravenous injection of 40 mg/kg vancomycin in 50 ml of lactated Ringer's solution were as follows: 30.17 +/- 20.68 micrograms/ml in the right (hypotonized) eyes and 4.92 +/- 3.33 micrograms/ml in the left (control) eyes. The difference in drug levels between the two sets of eyes had a high statistical significance at p = 0.001.

In Vivo Observations of the Episcleral Vasculature in the Albino Rabbit

The recently described arteriovenous anastomoses of the episcleral vasculature were studied in the albino rabbit by in vivo microscopy and microendoscopy. The arteriovenous anastomoses lead directly into the episcleral venous plexus which drains aqueous humor via well-visible aqueous veins. In the arteriolar segment of the arteriovenous anastomoses the blood flow velocity, measured by intra-arterial bolus injections of Evans blue, decreases drastically toward the venular segment of the arteriovenous anastomoses. After topical application of epinephrine, the arteriolar segment contracts faster and to a greater degree than all other parts of the episcleral vasculature. In the aqueous veins this stoppage of the blood inflow from the arteriovenous anastomoses may allow an increase in the amount of aqueous humor drained from the anterior chamber. The simultaneously measured intraocular pressure decreases significantly. Experimental elevation of the intraocular pressure from 18 to 30 mm Hg causes a decrease in diameter and blood flow in the arteriovenous anastomoses. These effects are reversed by returning to normal intraocular pressure levels. It is assumed that the arteriovenous anastomoses play a role in aqueous humor drainage by the episcleral venous plexus.

Immune-Related Disease and Normal-Tension Glaucoma

In Reply. —We are grateful to Dana and Wilensky and Hejkal and Yablonski for their careful and critical reading of our article. In designing our case-control study, we viewed the population as a continuum of people with varying degrees of susceptibility to damage from intraocular pressure. Those with unknown optic nerve susceptibility factors in high degree would develop NTG because their eyes are sensitive even to the normal level of intraocular pressure. In the middle ground are those who have high-tension glaucoma, having a more moderate amount of susceptibility factors, enough to make moderate elevation of the intraocular pressure harmful. Finally, at the other end of the spectrum are those ocular hypertensives so lacking in these susceptibility factors that they do not suffer damage even when challenged by elevated intraocular pressure. When looking for an explanation as to why some individuals are at one end of the spectrum and others

Peripapillary choroidal circulation in glaucoma.

Fluorescein angiography was performed at normal intraocular pressure levels and during induced ocular hypertension in glaucoma suspects and patients. Angiograms obtained at normal intraocular pressure levels in patients with glaucomatous cupping and visual field loss demonstrated either a delay in choroidal fluorescence that involved the entire choroid or, more frequently, a delay that involved a sharply outlined area of choroid near the temporal disc border. Angiography performed at intraocular pressures near 60 mm Hg in glaucoma suspects and patients with pathologic cupping revealed defects in peripapillary choroidal fluorescence. In patients without field loss, these defects were separated from the disc border by a rim of normally fluorescent choroid, whereas in patients with field loss, defects extended to the temporal disc border. These defects in peripapillary choroidal fluorescence are relevant to the development of visual field loss.