Biophysical Properties in Glaucoma: Diagnostic Technologies

This book provides an overview on new insights in glaucoma, the latest technological developments, scientific achievements, and novel research leading to new paradigms in glaucoma diagnosis. Readers will discover a broad picture starting from theoretical perspectives in diagnostic criteria followed by practical examination and clinical interpretations while highlighting potential pitfalls and limitations in analysis.  Non-invasive, modern technologies allowing visualization and quantification of various parts of the human eye are fast evolving and improving interpretation of modern diagnostic possibilities are essential to fill the gap between sophisticated equipment, complex clinical data, and the need for precision-medicine based interpretation. Issues such as the importance of intraocular, intracranial, and ocular perfusion pressures (IOP, ICP, OPP) in the pathogenesis of glaucoma; and imaging modalities for examination of the optic nerve head, retinal fiber layer, and visual field assessment in glaucoma are explored in these chapters. 

 

The problem-based learning approach presented herein offers a succinct go-to-guide to read and discover answers.​

• Language: English
• Publisher: Springer
• Release date: Jan 31, 2019
• ISBN: 9783319981987

Book preview

Part IImportance of Intraocular, Intracranial and Ocular Perfusion Pressures (IOP, ICP, OPP) in the Pathogenesis of Glaucoma

© Springer Nature Switzerland AG 2019

Ingrida Januleviciene and Alon Harris (eds.)Biophysical Properties in Glaucomahttps://doi.org/10.1007/978-3-319-98198-7_1

1. Intraocular Pressure as a Risk Factor

Lina Siaudvytyte¹  

(1)

Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania

Lina Siaudvytyte

Email: [e-mail]

Keywords

Intraocular pressureOpen-angle glaucoma

Intraocular pressure (IOP) is considered the main risk factor for the prevalence, incidence and progression of glaucoma [1–10]. Population-based epidemiologic studies indicate that the mean IOP is approximately 15.5 mmHg, with a standard deviation of nearly 3 mmHg [9–11]. This led to the definition of normal IOP as 2 standard deviations above and below the mean IOP, or approximately 10–21 mmHg [12]. The risk of glaucoma increases steadily with increasing IOP, starting even with IOP as low as 12 mmHg [10, 13–15]. Experimental studies showed that both acute IOP elevation or chronic IOP elevation in non-human primates caused posterior displacement of optic nerve and peripapillary tissue [16–18]. The Beaver Dam Eye Study revealed 5 mmHg difference in IOP between patients with glaucoma and those without [9]. The Baltimore Eye Survey demonstrated a fourfold increase in risk of development of glaucoma by 3 mmHg rise in IOP [10, 19]. Similarly, Suzuki et al. found that 4 mmHg rise in IOP increased risk for primary open-angle glaucoma (POAG) in twofold [20]. In the Barbados Eye Study, every increase of baseline IOP by 1 mmHg was associated with a 12% increased risk of glaucoma [21].

Large population-based studies showed that the level of IOP is a risk factor for glaucoma progression. (Table 1.1). The Collaborative Normal Tension Glaucoma Study (CNTGT) compared treatment versus no treatment in normal-tension glaucoma (NTG). Study results showed that a 30% reduction in IOP preserves the visual field progression in NTG [7]. The mean progression rate in the untreated subjects was 0.41 dB/year [22]. Early Manifest Glaucoma Trial (EMGT) compared treatment versus no treatment in open-angle glaucoma (OAG). Treated patients received a standardized treatment protocol of laser trabeculoplasty and topical betaxololum [3]. Study results showed that 1 mmHg reduction in IOP reduces risk of progression by approximately 10% [23]. Risk of progression was smaller with lower baseline IOP values and with a larger initial IOP drop induced by treatment [3]. Collaborative Initial Glaucoma Treatment Study (CIGTS) compared initial OAG treatment with medications versus filtration surgery [24]. IOP reduction was larger with surgery (48%, mean post treatment IOP 14–15 mmHg) compared with medications (35%, mean post treatment IOP 17–18 mmHg). 21% of surgical patients and 25% of medical patients had progressed after 8 years, defined as a worsening of visual field mean deviation by 3 dB [25]. Advanced Glaucoma Intervention Study (AGIS) compared argon laser trabeculoplasty (ATT) versus trabeculectomy (TAT) treatments in patients with advanced OAG [5]. ATT treatment included argon laser trabeculoplasty then if needed followed by trabeculectomy and then by second trabeculectomy. TAT treatment included trabeculectomy then argon laser trabeculoplasty if needed and then trabeculectomy. Study showed that surgical IOP lowering reduces the risk of glaucoma progression. Furthermore, there was no visual field progression in eyes with IOP <18 mmHg [5].

Table 1.1

Studies investigating relationship between intraocular pressure and glaucoma progression

AGIS Advanced Glaucoma Intervention Study, CIGTS Collaborative Initial Glaucoma Treatment Study, CNTGS The Collaborative Normal Tension Glaucoma Study, EGPS European Glaucoma Prevention Study, EMGT Early Manifest Glaucoma Trial, IOP intraocular pressure, NTG normal tension glaucoma, OAG open-angle glaucoma, OHT ocular hypertension, OHTS The Ocular Hypertension Treatment Study

In ocular hypertension (OHT) conversions to glaucoma occurs in only a small number of patients despite elevated IOP. The Ocular Hypertension Treatment Study (OHTS) compared treatment versus no treatment in OHT [2, 26]. 4.4% of OHT patients in the treated group had developed signs of glaucoma compared to 9% in controls after 5 years [2]. Thus >90% of untreated OHT patients had not converted to glaucoma after 5 years. European Glaucoma Prevention Study (EGPS) also compared treatment versus no treatment in OHT [27]. Patients were randomized into two groups: active therapy (dorzolamide) and placebo. The mean IOP reduction was 15% after 6 months and 22% after 5 years in the dorzolamide group, and accordingly, 9% and 19%, in placebo group [27].

IOP fluctuations also play an important role in glaucoma progression. The diurnal IOP fluctuation is defined as difference between the highest and lowest IOP in a single day. Short-term fluctuations are defined as periods of days to weeks, while long-term IOP fluctuations—periods of months to years. Diurnal IOP fluctuations up to 5 mmHg can occur in healthy subjects, while fluctuations 10–30 mmHg have been detected in untreated glaucoma patients [28]. Several studies reported that diurnal IOP fluctuations were higher in glaucomatous eyes compared to normal eyes [29, 30]. Most of these studies were limited by their retrospective analysis and lack of control for potentially confounding factors. Asrani et al. found that diurnal IOP fluctuation was a significant risk factor for glaucoma progression [31]. In contrast, Liu et al. did not find any significant difference in diurnal IOP fluctuations between untreated glaucomatous patients and healthy subjects [32]. Studies showed that a single short-term IOP fluctuation is likely to be of negligible significance, however the cumulative effect of constant or frequent IOP fluctuation could be significant in contributing to glaucoma pathogenesis [33]. The relationship between long-term IOP fluctuation and glaucoma progression is controversial [34–39]. Fukuchi et al. demonstrated that long-term IOP fluctuation was related with progression of glaucoma in NTG, while high IOP was more important in high-tension glaucoma (HTG) [35]. Lee et al. observed 4.2-fold increase in visual field progression for each 1 mmHg increase in long-term IOP fluctuation in NTG and OHT subjects [40]. Results from the Advanced Glaucoma Intervention Study (AGIS) showed that larger long-term IOP fluctuations were associated with progressive visual field deterioration [37]. In contrast, report from the Early Manifest Glaucoma Trial (EMGT) did not find any relationship between long-term IOP fluctuations and risk of glaucoma progression [36, 39].

References

1.

Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, et al. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943–53.Crossref

2.

Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol (Chicago, IL: 1960). 2002;120(6):701–30.Crossref

3.

Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol (Chicago, IL: 1960). 2003;121(1):48–56.Crossref

4.

Coleman AL, Caprioli J. The logic behind target intraocular pressure. Am J Ophthalmol. 2009;147:379–80.Crossref

5.

The Advanced Glaucoma Intervention Study (AGIS). The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429–40.Crossref

6.

Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126(4):487–97.Crossref

7.

Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126(4):498–505.Crossref

8.

Sommer A, Tielsch JM. Risk factors for open-angle glaucoma: the Barbados Eye Study. Arch Ophthalmol (Chicago, IL: 1960). 1996;114:235.Crossref

9.

Klein BE, Klein R, Linton KL. Intraocular pressure in an American community. The beaver dam eye study. Invest Ophthalmol Vis Sci. 1992;33(7):2224–8.PubMed

10.

Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol (Chicago, IL: 1960). 1991;109(8):1090–5.Crossref

11.

Bonomi L, Marchini G, Marraffa M, Bernardi P, De Franco I, Perfetti S, et al. Prevalence of glaucoma and intraocular pressure distribution in a defined population. The Egna-Neumarkt Study. Ophthalmology. 1998;105(2):209–15.Crossref

12.

Guidelines E. European Glaucoma Society terminology and guidelines for Glaucoma, 4th edition—part 1. Br J Ophthalmol. 2017.

13.

Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996;103(10):1661–9.Crossref

14.

Ramakrishnan R, Nirmalan PK, Krishnadas R, Thulasiraj RD, Tielsch JM, Katz J, et al. Glaucoma in a rural population of southern India: the Aravind comprehensive eye survey. Ophthalmology. 2003;110(8):1484–90.Crossref

15.

Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS, Mmbaga BB. Prevalence of glaucoma in a rural east African population. Invest Ophthalmol Vis Sci. 2000;41(1):40–8.PubMed

16.

Burgoyne CF, Downs JC, Bellezza AJ, Suh J-KF, Hart RT. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005;24(1):39–73.Crossref

17.

Heickell AG, Bellezza AJ, Thompson HW, Burgoyne CF. Optic disc surface compliance testing using confocal scanning laser tomography in the normal monkey eye. J Glaucoma. 2001;10(5):369–82.Crossref

18.

Yang H, Thompson H, Roberts MD, Sigal IA, Downs JC, Burgoyne CF. Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions. Invest Ophthalmol Vis Sci. 2011;52(1):345–63.Crossref

19.

Tielsch JM, Katz J, Singh K, Quigley HA, Gottsch JD, Javitt J, et al. A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. Am J Epidemiol. 1991;134(10):1102–10.Crossref

20.

Suzuki Y, Iwase A, Araie M, Yamamoto T, Abe H, Shirato S, et al. Risk factors for open-angle glaucoma in a Japanese population: the Tajimi study. Ophthalmology. 2006;113(9):1613–7.Crossref

21.

Leske MC, Wu S-Y, Hennis A, Honkanen R, Nemesure B. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115(1):85–93.Crossref

22.

Anderson DR, Drance SM, Schulzer M. Natural history of normal-tension glaucoma. Ophthalmology. 2001;108(2):247–53.Crossref

23.

Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol (Chicago, IL: 1960). 2002;120(10):1268–79.Crossref

24.

Musch DC, Gillespie BW, Niziol LM, Lichter PR, Varma R. Intraocular pressure control and long-term visual field loss in the collaborative initial Glaucoma treatment study. Ophthalmology. 2011;118(9):1766–73.Crossref

25.

Musch DC, Gillespie BW, Lichter PR, Niziol LM, Janz NK. Visual field progression in the collaborative initial Glaucoma treatment study the impact of treatment and other baseline factors. Ophthalmology. 2009;116(2):200–7.Crossref

26.

Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol (Chicago, IL: 1960). 2002;120(6):714–30.Crossref

27.

Miglior S, Zeyen T, Pfeiffer N, Cunha-Vaz J, Torri V, Adamsons I. Results of the European Glaucoma prevention study. Ophthalmology. 2005;112(3):366–75.Crossref

28.

Wallace J, Lovell HG. Glaucoma and intraocular pressure in Jamaica. Am J Ophthalmol. 1969;67(1):93–100.Crossref

29.

Sihota R, Saxena R, Gogoi M, Sood A, Gulati V, Pandey RM. A comparison of the circadian rhythm of intraocular pressure in primary phronic angle closure glaucoma, primary open angle glaucoma and normal eyes. Indian J Ophthalmol. 2005;53(4):243–7.Crossref

30.

Kim Y-K, Oh WH, Park KH, Kim JM, Kim DM. Circadian blood pressure and intraocular pressure patterns in normal tension glaucoma patients with undisturbed sleep. Korean J Ophthalmol. 2010;24(1):23–8.Crossref

31.

Asrani S, Zeimer R, Wilensky J, Gieser D, Vitale S, Lindenmuth K. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9(2):134–42.Crossref

32.

Liu JHK, Zhang X, Kripke DF, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis Sci. 2003;44(4):1586–90.Crossref

33.

Gardiner SK, Johnson CA, Demirel S. Factors predicting the rate of functional progression in early and suspected glaucoma. Invest Ophthalmol Vis Sci. 2012;53(7):3598–604.Crossref

34.

Leidl MC, Choi CJ, Syed ZA, Melki SA. Intraocular pressure fluctuation and glaucoma progression: what do we know? Br J Ophthalmol. 2014;98(10):1315–9.Crossref

35.

Fukuchi T, Yoshino T, Sawada H, Seki M, Togano T, Tanaka T, et al. The relationship between the mean deviation slope and follow-up intraocular pressure in open-angle glaucoma patients. J Glaucoma. 2013;22(9):689–97.Crossref

36.

Medeiros FA, Weinreb RN, Zangwill LM, Alencar LM, Sample PA, Vasile C, et al. Long-term intraocular pressure fluctuations and risk of conversion from ocular hypertension to glaucoma. Ophthalmology. 2008;115(6):934–40.Crossref

37.

Nouri-Mahdavi K, Hoffman D, Coleman AL, Liu G, Li G, Gaasterland D, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627–35.Crossref

38.

Naito T, Yoshikawa K, Mizoue S, Nanno M, Kimura T, Suzumura H, et al. Relationship between progression of visual field defect and intraocular pressure in primary open-angle glaucoma. Clin Ophthalmol. 2015;9:1373–8.Crossref

39.

Bengtsson B, Leske MC, Hyman L, Heijl A. Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(2):205–9.Crossref

40.

Lee PP, Walt JW, Rosenblatt LC, Siegartel LR, Stern LS. Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. Am J Ophthalmol. 2007;144(6):901–7.Crossref

© Springer Nature Switzerland AG 2019

Ingrida Januleviciene and Alon Harris (eds.)Biophysical Properties in Glaucomahttps://doi.org/10.1007/978-3-319-98198-7_2

2. Intracranial Pressure as a Risk Factor

Lina Siaudvytyte¹  

(1)

Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania

Lina Siaudvytyte

Email: [e-mail]

Contemplations of intracranial pressure (ICP) role in glaucoma started in 1908 by Noishevsky and were confirmed later experimentally with animals [1–5]. Optic nerve head is located at the junction between the relatively high-pressure intraocular space and low-pressure subarachnoid space, therefore pressure imbalance between these two regions may be the cause of damage of retinal ganglion cells axons that cross the lamina cribrosa. As such, ICP can influence the biomechanics of the lamina cribrosa and peripapillary sclera [1–3].

Physiological values of ICP varies with body posture but is generally considered to be 5–15 mmHg in healthy supine adults, 3–7 mmHg in children and 1.5–6 mmHg in infants [6–9]. Head elevation decreases ICP by displacing cerebrospinal fluid (CSF) into the spinal canal and by improving cerebral venous drainage by opening alternative venous channels in the posterior circulation that remain closed while patients remain recumbent. Experimental studies showed that ICP in the sitting position at the level of the occipital prominence, equivalent to eye level, ranges between 0 and −10 mmHg [10]. Fleischman et al. found that ICP is stable (11.5 (2.8) mmHg) for the first 50 years of life after which there is a steady decline [11]. Pederson et al. found similar results concluding that ICP decreases by 0.69 mmHg per decade [12]. Furthermore, CSF secretion by the choroid plexuses slows with age, reducing the rate of CSF turnover and leading to accumulation of catabolites in the brain and CSF [13–15]. Interestingly, the prevalence of glaucoma increases with age [16]. Contrarily, other studies failed to find a relationship between age and ICP [17–20]. Various studies revealed that body mass index is positively associated with ICP [21–23].