Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes

doi:10.1016/j.ophtha.2014.01.017

Ophthalmology

Volume 121, Issue 7, July 2014, Pages 1350-1358

https://doi.org/10.1016/j.ophtha.2014.01.017 Get rights and content

Purpose

To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD.

Design

Prospective, observational cohort study.

Participants

Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.

Methods

Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables.

Main Outcome Measures

The rate of RNFL thinning and the probability of developing VFD.

Results

Four hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2–9), with median follow-up of 2.2 years (0.4–4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (−2.02 μm/year vs. −0.82 μm/year; P < 0.001). The joint longitudinal survival model showed that each 1-μm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14–3.71; P = 0.017).

Conclusions

The rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-μm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

Section snippets

Study Design

Subjects were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. The study design has been described in detail previously.³² In brief, participants in these studies were evaluated every 6 months, in which patients underwent extensive predetermined clinical examinations. Inclusion criteria for these studies were open angles, a best-corrected visual acuity of 20/40 or better, a spherical refraction within ±5.0 diopters (D), and

Study Population

Four hundred fifty-four eyes of 294 glaucoma suspects were included. One hundred eighty-three patients (62.2%) were women. Mean age ± standard deviation at baseline was 64.5±11.3 years. Ninety-two subjects (31.3%) were of African descent and 202 subjects (68.7%) were of European descent. At the baseline examination, 239 eyes (52.6%) were categorized as having ocular hypertension. The average number of OCT examinations per eye was 4.6 (range, 2–9), with median follow-up of 2.2 years.

Baseline Factors

Forty eyes

Discussion

In this cohort of glaucoma suspects followed up for a relatively short period (2.2 years), eyes in which VFD developed had an approximately 2.5-times faster rate of RNFLT loss compared with eyes that did not develop VFD. Moreover, a 1-μm/year faster rate of RNFL loss resulted in a 2.05-times higher risk of developing VFD. These results suggest that the rate of RNFL loss measured with SD-OCT may be useful for identifying which glaucoma suspect patients are at the highest risk of developing VFD.

References (61)

R.N. Weinreb et al.
Primary open-angle glaucoma
Lancet
(2004)
P.H. Artes et al.
Longitudinal changes in the visual field and optic disc in glaucoma
Prog Retin Eye Res
(2005)
T. Fayers et al.
Monitoring glaucomatous progression using a novel Heidelberg Retina Tomograph event analysis
Ophthalmology
(2007)
C.K. Leung et al.
Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: patterns of retinal nerve fiber layer progression
Ophthalmology
(2012)
J.L. See et al.
Rates of neuroretinal rim and peripapillary atrophy area change: a comparative study of glaucoma patients and normal controls
Ophthalmology
(2009)
C.K. Leung et al.
Evaluation of retinal nerve fiber layer progression in glaucoma: a prospective analysis with neuroretinal rim and visual field progression
Ophthalmology
(2011)
C.K. Leung et al.
Evaluation of retinal nerve fiber layer progression in glaucoma: a comparison between spectral-domain and time-domain optical coherence tomography
Ophthalmology
(2011)
B.C. Chauhan et al.
Incidence and rates of visual field progression after longitudinally measured optic disc change in glaucoma
Ophthalmology
(2009)
M.E.J. van Velthoven et al.
Recent developments in optical coherence tomography for imaging the retina
Prog Retin Eye Res
(2007)
F.A. Medeiros et al.
Evaluation of progressive neuroretinal rim loss as a surrogate end point for development of visual field loss in glaucoma
Ophthalmology
(2014)

E.J. Lee et al.

Ability of Stratus OCT to detect progressive retinal nerve fiber layer atrophy in glaucoma

Invest Ophthalmol Vis Sci

(2009)

N.G. Strouthidis et al.

Optic disc and visual field progression in ocular hypertensive subjects: detection rates, specificity, and agreement

Invest Ophthalmol Vis Sci

(2006)

Cited by (155)

The Impact of Achieving Target Intraocular Pressure on Glaucomatous Retinal Nerve Fiber Layer Thinning in a Treated Clinical Population
2024, American Journal of Ophthalmology
To estimate the effect of being below and above the clinician-set target intraocular pressure (IOP) on rates of glaucomatous retinal nerve fiber layer (RNFL) thinning in a treated real-world clinical population.
Retrospective cohort study.
A total of 3256 eyes (1923 patients) with ≥5 reliable optical coherence tomography scans and 1 baseline visual field test were included. Linear mixed-effects modeling estimated the effects of the primary independent variables (mean target difference [measured IOP – target IOP] and mean IOP, mm Hg) on the primary dependent variable (RNFL slope, µm/y) while accounting for additional confounding variables (age, biological sex, race, baseline RNFL, baseline pachymetry, and disease severity). A spline term accounted for differential effects when above (target difference >0 mm Hg) and below (target difference ≤0 mm Hg) target pressure.
Eyes below and above target had significantly different mean RNFL slopes (–0.44 vs –0.71 µm/y, P < .001). Each 1 mm Hg increase above target had a 0.143 µm/y faster rate of RNFL thinning (P < .001). Separating by disease severity, suspect, mild, moderate, and advanced glaucoma had 0.135 (P = .002), 0.116 (P = .009), 0.203 (P = .02), and 0.65 (P = .22) µm/y faster rates of RNFL thinning per 1 mm Hg increase, respectively.
Being above the clinician-set target pressure is associated with more rapid RNFL thinning in suspect, mild, and moderate glaucoma. Faster rates of thinning were also present in advanced glaucoma, but statistical significance was limited by the lower sample size of eyes above target and the optical coherence tomography floor effect.
A novel convolutional neural network for identification of retinal layers using sliced optical coherence tomography images
2024, Healthcare Analytics
Retinal imaging is crucial for observing the retina and accurately diagnosing pathological problems. Optical Coherence Tomography (OCT) has been a transformative breakthrough for developing high-resolution cross-sectional images. It is imperative to delineate the multiple layers of the retina for a proper diagnosis. A novel segmentation-based approach is introduced in this study to identify seven distinct layers of the retina using OCT images. The developed approach presents SliceOCTNet, a customized U-shaped Convolutional Neural Network (CNN) that introduces group normalization and intricate skip connections. Paired alongside a hybrid loss function, the SliceOCTNet outperformed most state-of-the-art approaches. The introduction of Group Normalization in SliceOCTNet stabilized the model and improved layer identification even when working with small datasets. The use of skip connections also contributed to an improvement in the spatial outlook of the model. Implementing a hybrid loss function addresses the class imbalance problem in the dataset. Duke University’s spectral-domain optical coherence tomography (SD-OCT) B-scan dataset of healthy and Diabetic Macular Edema (DME) afflicted patients was utilized to train and evaluate the SliceOCTNet. The model accurately recognizes the seven layers of the retina. It can achieve a high dice coefficient value of 0.941 and refine the segmentation process to a higher level of precision.
Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents
2024, American Journal of Ophthalmology
To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED).
Retrospective cohort study.
AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort–specific RNFLT baseline/thinning rates).
We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (–0.8 vs –0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%).
Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races.
Secondhand smoke exposure and ocular health: A systematic review
2023, Survey of Ophthalmology
The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms—supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health.
Endpoints for clinical trials in ophthalmology
2023, Progress in Retinal and Eye Research
With the identification of novel targets, the number of interventional clinical trials in ophthalmology has increased. Visual acuity has for a long time been considered the gold standard endpoint for clinical trials, but in the recent years it became evident that other endpoints are required for many indications including geographic atrophy and inherited retinal disease. In glaucoma the currently available drugs were approved based on their IOP lowering capacity. Some recent findings do, however, indicate that at the same level of IOP reduction, not all drugs have the same effect on visual field progression. For neuroprotection trials in glaucoma, novel surrogate endpoints are required, which may either include functional or structural parameters or a combination of both. A number of potential surrogate endpoints for ophthalmology clinical trials have been identified, but their validation is complicated and requires solid scientific evidence. In this article we summarize candidates for clinical endpoints in ophthalmology with a focus on retinal disease and glaucoma. Functional and structural biomarkers, as well as quality of life measures are discussed, and their potential to serve as endpoints in pivotal trials is critically evaluated.
Comparing Rates of Change in Moderate to Advanced Glaucoma: Retinal Nerve Fiber Layer Versus Bruch Membrane Opening-Minimum Rim Width
2023, American Journal of Ophthalmology
To compare rates of change (RoC) of peripapillary retinal nerve fiber layer (RNFL) and Bruch membrane opening-based minimum rim width (BMO-MRW) thickness in moderate-to-advanced glaucoma.
Prospective cohort study.
Longitudinal optical coherence tomography (OCT) optic nerve head volume scans of 113 eyes of 113 glaucoma patients with moderate-to-advanced or central damage were exported. This study estimated and compared global and sectoral RoC with linear mixed effects models and simple linear regression (SLR) of RNFL and BMO-MRW thickness. Permutation analyses were used to test significance of RoC in the SLR model. It also compared longitudinal signal-to-noise ratios (LSNR) defined as RoC divided by residual standard deviation (SD) between the two groups.
Mean (SD) follow-up and median (IQR) OCT scan sessions were 5.2 (1.3) years and 10 (8-11), respectively. Baseline average (SD) visual field mean deviation was –9.2 (5.8) dB. Based on SLR, a higher proportion of significant negative RNFL RoC was observed compared to BMO-MRW in the inferotemporal (35% vs 20%; P = .015) and inferonasal (42% vs 17%; P < .001) sectors. Permutation analyses also demonstrated a higher proportion of worsening RNFL RoC than BMO-MRW in the inferotemporal (P = .026) and inferonasal (P < .001) sectors along with overall lower positive RoC. Longitudinal signal-to-noise ratios for RNFL were significantly more negative than for BMO-MRW globally, and in the inferotemporal, inferonasal, and superonasal sectors (P ≤ .01).
Longitudinal RNFL OCT measurements are more likely to detect structural change and demonstrate better LSNR compared with BMO-MRW in eyes with central or moderate-to-advanced glaucoma damage at baseline.

View all citing articles on Scopus

Financial Disclosure(s): The author(s) have made the following disclosure(s):

Atsuya Miki: Financial support – Nidek

Felipe A. Medeiros: Financial support – Carl-Zeiss Meditec, Heidelberg Engineering, Topcon, Inc.

Robert N. Weinreb: Financial support – Nidek, Topcon, Zeiss Meditec, Alcon, Allergan, Bausch & Lomb; Nonfinancial support – Heidelberg Engineering; Patent - RGC Index

Jeffrey M. Liebmann: Financial support – Carl Zeiss Meditec, Topcon, Inc., Alcon Laboratories, Allergan, Inc, Diopsys Corporation, Glaukos Corporation, Heidelberg Engineering, Merz Pharmaceutical, Inc, Optovue, Inc, Quark Pharmaceuticals, Inc, SOLX, Inc.

Christopher A. Girkin: Financial support – Carl Zeiss Meditech, Inc, Heidelberg Engineering.

Linda M. Zangwill: Nonfinancial support – Heidelberg Engineering, Carl Zeiss Meditec, Topcon, Inc.

Alcon Laboratories, Inc., Allergan, Inc, Pfizer, Inc., Merck, Inc, and Santen, Inc, provided the participants' glaucoma medications at no charge.

: Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant nos.: P30EY022589 (L.M.Z.), U10EY14267 (L.M.Z.) EY019869 (L.M.Z.), EY021818 (F.A.M.), EY022039 (C.B.), EY08208 (F.A.M.), EY11008 (L.M.Z.), and EY13959) (C.A.G.); Eyesight Foundation of Alabama, Birmingham, AL (C.A.G.); the Edith C. Blum Research Fund of the New York Glaucoma Research Institute, New York, New York (J.M.L.); Japan Eye Bank Association, Tokyo, Japan (Overseas Research Grant [A.M.]); Research to Prevent Blindness, Inc., New York, New York (unrestricted grant) (R.N.W.).

View full text

Original articleRates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Study Design

Study Population

Baseline Factors

Discussion

Lancet

Prog Retin Eye Res

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Prog Retin Eye Res

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Jpn J Ophthalmol

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

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

Results of the European Glaucoma Prevention Study

Ophthalmology

Differential light threshold: short- and long-term fluctuation in patients with glaucoma, normal controls, and patients with suspected glaucoma

Arch Ophthalmol

Effect of instructions on conventional automated perimetry

Invest Ophthalmol Vis Sci

Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season

Invest Ophthalmol Vis Sci

Approach for identifying glaucomatous optic nerve progression by scanning laser tomography

Invest Ophthalmol Vis Sci

Optimizing and validating an approach for identifying glaucomatous change in optic nerve topography

Invest Ophthalmol Vis Sci

A new statistical approach for quantifying change in series of retinal and optic nerve head topography images

Invest Ophthalmol Vis Sci

Optical coherence tomography longitudinal evaluation of retinal nerve fiber layer thickness in glaucoma

Arch Ophthalmol

Ability of Stratus OCT to detect progressive retinal nerve fiber layer atrophy in glaucoma

Invest Ophthalmol Vis Sci

Optic disc and visual field progression in ocular hypertensive subjects: detection rates, specificity, and agreement

Invest Ophthalmol Vis Sci

Original article
Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes