Corneal Hysteresis as a Risk Factor for Glaucoma Progression: A Prospective Longitudinal Study

doi:10.1016/j.ophtha.2013.01.032

Ophthalmology

Volume 120, Issue 8, August 2013, Pages 1533-1540

https://doi.org/10.1016/j.ophtha.2013.01.032 Get rights and content

Purpose

To evaluate the role of corneal hysteresis (CH) as a risk factor for the rate of visual field progression in a cohort of patients with glaucoma followed prospectively over time.

Design

Prospective observational cohort study.

Participants

The study group included 114 eyes of 68 patients with glaucoma followed for an average of 4.0±1.1 years. Visual fields were obtained with standard automated perimetry. Included eyes had a median number of 7 (range, 5–12) tests during follow-up.

Methods

The CH measurements were acquired at baseline using the Ocular Response Analyzer (Reichert Instruments, Depew, NY). Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). Linear mixed models were used to investigate the relationship between rates of visual field loss and baseline CH, baseline intraocular pressure (IOP), and central corneal thickness (CCT), while adjusting for potentially confounding factors. An interaction term between IOP and CH was included in the model to investigate whether the effect of IOP on rates of progression depended on the level of CH.

Main Outcome Measures

Effects of CH, IOP, and CCT on rates of VFI loss over time.

Results

The CH had a significant effect on rates of visual field progression over time. In the univariable model including only CH as a predictive factor along with time and their interaction, each 1 mmHg lower CH was associated with a 0.25%/year faster rate of VFI decline over time (P < 0.001). The multivariable model showed that the effect of IOP on rates of progression depended on CH. Eyes with high IOP and low CH were at increased risk for having fast rates of disease progression. The CH explained a larger proportion of the variation in slopes of VFI change than CCT (17.4% vs. 5.2%, respectively).

Conclusions

The CH measurements were significantly associated with risk of glaucoma progression. Eyes with lower CH had faster rates of visual field loss than those with higher CH. The prospective longitudinal design of this study supports the role of CH as an important factor to be considered in the assessment of the risk of progression in patients with glaucoma.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Materials and Methods

This was an observational cohort study. Participants from this study were included in a prospective longitudinal study designed to evaluate optic nerve structure and visual function in glaucoma (Diagnostic Innovations in Glaucoma Study [DIGS]) conducted at the Hamilton Glaucoma Center, University of California, San Diego. Participants in the DIGS were longitudinally evaluated according to a pre-established protocol that included regular follow-up visits in which patients underwent clinical

Results

The study included 114 eyes of 68 patients with glaucoma followed for an average of 4.0±1.1 years (range, 2.0–6.5 years). Included eyes had a median number of 7 (range, 5–12) visual field tests during follow-up. Table 1 shows baseline clinical and demographic information for the eyes included in the study. Figure 1 shows a scatterplot matrix illustrating the relationship among GAT IOP, CCT, and CH. The GAT IOP was significantly influenced by CCT (r=0.36; P < 0.001) but not by CH (r=0.01; P

Discussion

In the current study, we demonstrated that CH was significantly associated with the rate of visual field loss in a cohort of patients with glaucoma followed over time. Eyes with lower baseline hysteresis tended to progress significantly faster than those with higher hysteresis values. Such relationship was present even in a multivariable model adjusting for other factors known to potentially affect rates of glaucoma progression. To our knowledge, this is the first prospective longitudinal study

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Cited by (223)

Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study
2024, Ophthalmology
To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study.
Randomized, double-masked, placebo-controlled multicenter trial.
Participants with ≥5 VFs (213 placebo, 217 treatment).
Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms.
Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations.
In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, –0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, –0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 μm thicker; P = 0.01) and normalized OPA (estimate, –3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, –0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression.
No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
The pre-Descemet's layer (Dua's layer, also known as the Dua-Fine layer and the pre-posterior limiting lamina layer): Discovery, characterisation, clinical and surgical applications, and the controversy
2023, Progress in Retinal and Eye Research
The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 μm (range 6–16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals.
The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK.
The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations.
Five-Year Visual Field Outcomes of the HORIZON Trial
2023, American Journal of Ophthalmology
To compare visual field (VF) progression between glaucoma patients receiving cataract surgery alone (CS) or with a Hydrus microstent (CS-HMS).
Post hoc analysis of VF data from the HORIZON multicenter randomized controlled trial.
A total of 556 patients with glaucoma and cataract were randomized 2:1 to either CS-HMS (369) or CS (187) and followed up for 5 years. VF was performed at 6 months and then every year after surgery. We analyzed data for all participants with at least 3 reliable VFs (false positives < 15%). Average between-group difference in rate of progression (RoP) was tested using a Bayesian mixed model and a 2-sided Bayesian P value <.05 (main outcome). A multivariable model measured the effect of intraocular pressure (IOP). A survival analysis compared the probability of global VF sensitivity dropping by predefined cutoffs (2.5, 3.5, 4.5, and 5.5 dB) from baseline.
Data from 352 eyes in the CS-HMS arm and 165 in the CS arm were analyzed (2966 VFs). The mean RoP was –0.26 dB/y (95% credible interval –0.36, –0.16) for CS-HMS and –0.49 dB/y (95% credible interval –0.63, –0.34) for CS. This difference was significant (P = .0138). The difference in IOP only explained 17% of the effect (P < .0001). Five-year survival analysis showed an increased probability of VF worsening by 5.5 dB (P = .0170), indicating a greater proportion of fast progressors in the CS arm.
CS-HMS has a significant effect on VF preservation in glaucoma patients compared with CS alone, reducing the proportion of fast progressors.
Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology
2023, Ophthalmology
To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients.
Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded.
Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP.
Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients.
Proprietary or commercial disclosure may be found after the references.
Effect of Corneal Hysteresis on the Rates of Microvasculature Loss in Glaucoma
2023, Ophthalmology Glaucoma
To investigate the association between corneal hysteresis (CH) and rates of optic nerve head whole image capillary density (wiCD) loss over time in open-angle glaucoma (OAG).
Observational cohort.
One hundred seventy-four eyes (122 OAG and 52 glaucoma suspect eyes) from 112 patients over more than 2 years and 4 visits or more.
Baseline CH measurements were acquired with the Ocular Response Analyzer. Linear mixed-effect models were designed to investigate the effect of CH, average intraocular pressure (IOP) during follow-up, and baseline visual field (VF) mean deviation (MD) on the rates of wiCD loss and circumpapillary retinal nerve fiber layer (cpRNFL) thinning over time, while adjusting for confounders. Interaction between CH or baseline MD and average IOP during follow-up were included in final models to evaluate the effect of baseline MD or average IOP during follow-up on structural changes for different values of CH.
Effect of CH, IOP, and baseline MD on the rates of wiCD loss and cpRNFL thinning over time.
The average follow-up time was 3.9 years. In the multivariable model, non-Black race, higher average IOP during follow-up, lower baseline CH, lower baseline VF MD, and higher numbers of IOP-lowering medications were associated with faster rates of wiCD loss over time. For CH values 6 mmHg and 12 mmHg, every 1-mmHg increase in average IOP during follow-up was associated with 0.23% per year faster and 0.07% per year slower rates of wiCD loss over time, respectively. While every 1-mmHg decrease in CH was associated with 1.89% per year faster rate of wiCD loss for MD of –12 dB, it was associated with 0.81% per year faster rate of wiCD loss for MD of –3 dB.
Lower CH values were significantly associated with faster rates of wiCD loss over time. In eyes with lower CH, both higher average IOP during follow-up and more severe glaucoma damage at baseline were associated with faster rates of wiCD loss and cpRNFL thinning. These results support CH as a useful parameter for risk assessment of glaucoma progression.
Proprietary or commercial disclosure may be found after the references.
In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus
2024, International Ophthalmology

View all citing articles on Scopus

: Manuscript no. 2012-1597.

: Financial Disclosure(s): The author(s) have made the following disclosure(s): FAM has received research support from Reichert, Inc, and Carl Zeiss Meditec, Inc. LMZ and RNW have received research support from Carl Zeiss Meditec, Inc. RNW is a consultant to Carl Zeiss Meditec, Inc.

: Supported in part by National Institutes of Health/National Eye Institute Grants EY021818 (F.A.M.), EY11008 (L.M.Z.), and EY14267 (L.M.Z.); CAPES Grant BEX 1066/11-0; an unrestricted grant from Research to Prevent Blindness (New York, NY); and grants for participants' glaucoma medications from Alcon, Allergan, Pfizer, Merck, and Santen.

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Original articleCorneal Hysteresis as a Risk Factor for Glaucoma Progression: A Prospective Longitudinal Study

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Materials and Methods

Results

Discussion

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

J Cataract Refract Surg

Ophthalmology

Am J Ophthalmol

Prog Retin Eye Res

Natural history of normal-tension glaucoma

Ophthalmology

Who should be treated?

Results of the European Glaucoma Prevention Study

Ophthalmology

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

The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration

Am J Ophthalmol

The relationship between intraocular pressure and progressive retinal nerve fiber layer loss in glaucoma

Ophthalmology

The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma

Arch Ophthalmol

Central corneal thickness and thickness of the lamina cribrosa and peripapillary sclera in monkeys

Arch Ophthalmol

Central corneal thickness and thickness of the lamina cribrosa in human eyes

Invest Ophthalmol Vis Sci

Lower corneal hysteresis is associated with more rapid glaucomatous visual field progression

J Glaucoma

Original article
Corneal Hysteresis as a Risk Factor for Glaucoma Progression: A Prospective Longitudinal Study