Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: A Prospective Analysis of Age-Related Loss

doi:10.1016/j.ophtha.2011.10.010

Ophthalmology

Volume 119, Issue 4, April 2012, Pages 731-737

https://doi.org/10.1016/j.ophtha.2011.10.010 Get rights and content

Objective

To investigate age-related changes of the retinal nerve fiber layer (RNFL) imaged by a spectral-domain optical coherence tomography (OCT).

Design

Prospective, cross-sectional, and longitudinal studies.

Participants

One hundred normal individuals were recruited for cross-sectional analysis, 35 of whom were randomly selected for longitudinal analysis.

Methods

The circumpapillary average and quadrant RNFL thicknesses were measured by the Cirrus HD-OCT. In the longitudinal study, participants were followed at 4-month intervals for a mean of 30 months (range, 24–41 months) for RNFL and visual field measurements. Cross-sectional RNFL data were analyzed with multiple linear regression models with adjustment of spherical error, optic disc area, and signal strength. Longitudinal RNFL measurements were analyzed with linear mixed models with fixed coefficients on follow-up duration, baseline RNFL thickness, spherical error, optic disc area, and signal strength. Factors influencing the rate of change of RNFL measurements were analyzed in the interaction terms with “duration” in the linear mixed models.

Main Outcome Measures

Rates of change of average and quadrant RNFL thicknesses.

Results

In the cross-sectional analysis, significant negative correlations were found between age and average (−0.33 μm/year; P = 0.011), inferior (−0.45 μm/year; P = 0.037), and temporal (−0.31 μm/year; P = 0.046) RNFL thicknesses. In the longitudinal analysis, the mean rates of change of average, superior, and inferior RNFL thicknesses were −0.52 (95% confidence interval [CI], −0.86 to −0.17), −1.35 (95% CI, −2.05 to −0.65) and −1.25 μm/year (95% CI, −1.78 to −0.71), respectively, after adjusting for baseline RNFL thickness, spherical error, disc area, and signal strength. There was no detectable RNFL reduction in the nasal and temporal quadrants. The only significant factor influencing the rates of change of RNFL measurements was the baseline RNFL thickness. A greater baseline RNFL thickness was associated with a faster rate of change.

Conclusions

Progressive, age-related decline of RNFL thickness can be detected with longitudinal OCT imaging. Rate estimates derived from trend analysis for detection of glaucomatous RNFL progression should be interpreted with reference to the normal ranges of age-related reduction, particularly when the baseline RNFL measurement is large.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Subjects

One hundred normal Hong Kong Chinese examined in the University Eye Center, Hong Kong Eye Hospital, were consecutively enrolled for the research study “RNFL imaging with spectral-domain OCT.” Thirty-five were randomly selected and agreed to be followed every 4 months for ≥24 months. Normal individuals had best-corrected visual acuity of ≥20/40 with spherical error between +6.00 and −6.00 diopters for both eyes. They had no visual field defect, no structural optic disc abnormalities, no history

Results

One hundred healthy, normal individuals were included in the cross-sectional study, 35 of whom were randomly selected and agreed to participate in the longitudinal study. They had regular follow-up at 4-month intervals for measurement of the RNFL and visual field examination. No individuals developed visual field defects in the latest follow-up visit. Participants in the cross-sectional and the longitudinal studies did not differ in age, spherical error, central corneal thickness, and baseline

Discussion

To our knowledge, this is the first study investigating age-related change of the RNFL with a prospective, longitudinal study design. This study confirms that there is an age-related decline of the RNFL. More important, the reporting of the rate of change of the RNFL in normal eyes is clinically relevant in discriminating physiologic from pathologic degeneration of the optic nerve when evaluating glaucoma progression. After adjusting the potential confounding variables of RNFL measurement,

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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.
Optical coherence tomography as a potential surrogate marker of dopaminergic modulation across the life span
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The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation of the retina, shows promise to be used as a surrogate marker of dopaminergic neuromodulation in cognition. Overall, most evidence supports reduced retinal thickness in individuals with dopaminergic dysregulation (e.g., patients with Parkinson’s Disease, non-demented older adults) and with poor cognitive functioning. By using the theoretical framework of metacontrol, we derive hypotheses that retinal thinning associated to decreased dopamine (DA) levels affecting D1 families, might lead to a decrease in the signal-to-noise ratio (SNR) affecting cognitive persistence (depending on D1-modulated DA activity) but not cognitive flexibility (depending on D2-modulated DA activity). We argue that the use of OCT parameters might not only be an insightful for cognitive neuroscience research, but also a potentially effective tool for individualized medicine with a focus on cognition. As our society progressively ages in the forthcoming years and decades, the preservation of cognitive abilities and promoting healthy aging will hold of crucial significance. OCT has the potential to function as a swift, non-invasive, and economical method for promptly recognizing individuals with a heightened vulnerability to cognitive deterioration throughout all stages of life.
Progressive Changes in the Neuroretinal Rim and Retinal Nerve Fiber Layer in Glaucoma: Impact of Baseline Values and Floor Effects
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To determine whether more severe baseline damage impedes measurement of minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (RNFLT) change in glaucoma patients because of a floor effect.
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Baseline global and sectorial MRW and RNFLT values were classified as within normal limits, borderline, or outside normal limits based on reference normative values. Regression analysis was used to determine the magnitude and significance of MRW and RNFLT change. Additionally, the follow-up period for each participant was divided into 2 equal halves (first and second periods) to determine whether there was attenuation of MRW and RNFLT change with follow-up time.
Rates of global and sectoral MRW and RNFLT changes (slopes).
A total of 97 patients with glaucoma (median age, 70.3 years) and 42 healthy subjects (median age, 64.8 years) were followed for a median of 6.9 years and 7.0 years, respectively. The median mean deviation of the visual field in glaucoma patients was –4.30 decibels (dB) (interquartile range, –7.81 to –2.06 dB; range, –20.68 to 1.37 dB). Statistically significant changes in global and sectoral MRW and RNFLT were detected across all baseline classifications; however, there was a tendency for less change with increasing baseline damage. In glaucoma patients, RNFLT slopes, but not MRW slopes, were significantly more positive (less change) in the second period compared with the first. There were also no differences in MRW or RNFLT slopes in the first and second periods in healthy subjects.
Significant MRW and RNFLT changes were detected at all levels of baseline damage. However, an attenuation in the rate of RNFLT change compared with MRW indicates an earlier floor effect in RNFLT measurements globally and in equivalent sectors. Because the axonal component of these measurements should be equivalent, our results suggest important differences in tissue remodeling at the level of the optic nerve head and peripapillary retina.
Proprietary or commercial disclosure may be found after the references.
Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension
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To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results.
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Six hundred eyes of 306 patients with OHT.
All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis.
Prevalence of RNFL defects.
The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch’s membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01–3.29), cup volume (mm³) (OR, 1.24; 95% CI, 1.01–1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01–1.07) were associated with RNFL defects.
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Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Citation Excerpt :
The results found in a cross-sectional study ranged between -0.16 µm/year and -0.33 µm/year. On the other hand, a longitudinal analysis found a mean rate of -0.52 µm/year.[11], [43], [50] Regarding the age-related loss of neuroretinal rim area, different results were observed, ranging from -1.25 × 10−3 [58] to -2.5 × 10−3 mm²/year[23].
Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful in slowing disease progression, little is known about the natural history of untreated glaucoma. This knowledge can be valuable in guiding management decisions in the era of personalized medicine. A systematic search was performed in Medline (PubMed), Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRIMSA) guidelines. The rate of structural and/or functional progression and conversion to glaucoma or to a more advanced stage of glaucoma are discussed for ocular hypertension and different types of open-angle glaucoma. Forty-three studies were included. Different rates of progression were found both among and within the different diagnostic groups that belong to the open-angle glaucoma spectrum. The highest rate was found in pseudoexfoliation glaucoma, followed by high tension glaucoma, normal tension glaucoma, and ocular hypertension, in decreasing order. The lowest rate was observed in glaucoma suspects. The known rates of progression provide valuable prognostic information for ophthalmologists and patients. Nonetheless, due to high variability among patients, individual progression cannot be accurately predicted and repeated follow-up examinations are required to estimate individual progression.
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Ofrecer una serie de recomendaciones generales que sirvan de orientación en la evaluación y el manejo de la progresión glaucomatosa en la práctica clínica diaria a partir de la evidencia clínica de calidad existente.
Tras la definición de los objetivos y del alcance de la guía se constituyó el grupo de trabajo que formuló las preguntas clínicas estructuradas siguiendo el formato PICO (Patient, Intervention, Comparison, Outcomes). Una vez evaluada toda la evidencia clínica existente con las herramientas AMSTAR 2 (Assessment of Multiple systematic Rewiews) y Risk of bias de Cochrane de forma independiente por al menos dos revisores, se pasó a la formulación de recomendaciones siguiendo la metodología del Scottish Intercollegiate Guideline Network (SIGN).
Se presentan recomendaciones con sus correspondientes niveles de evidencia que pueden ser de utilidad para la detección y el seguimiento de la progresión glaucomatosa con los distintos métodos disponibles y para el tratamiento de los pacientes.
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To provide general recommendations that serve as a guide for the evaluation and management of glaucomatous progression in daily clinical practice based on the existing quality of clinical evidence.
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View all citing articles on Scopus

: Manuscript no. 2011-1022.

: Financial Disclosure(s): The authors have made the following disclosures:

: Christopher Leung – Speaker honorarium – Carl Zeiss Meditec, Heidelberg Engineering, Topcon; Research support – Carl Zeiss Meditec, Optovue.

: Robert N. Weinreb – Consultant – Carl Zeiss Meditec, Optovue; Research support – Heidelberg Engineering, Topcon, Nidek.

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Original articleRetinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: A Prospective Analysis of Age-Related Loss

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Subjects

Results

Discussion

Neurobiol Aging

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Surv Ophthalmol

Aging of the human retina: differential loss of neurons and retinal pigment epithelial cells

Invest Ophthalmol Vis Sci

Neuronal density in the human retinal ganglion cell layer from 16-77 years

Anat Rec

Number of neurons in the retinal ganglion cell layer of the quokka wallaby do not change throughout life

Anat Rec

Human optic nerve fiber count and optic disc size

Invest Ophthalmol Vis Sci

Peripapillary retinal nerve fiber layer thickness determined by spectral-domain optical coherence tomography in ophthalmologically normal eyes

Arch Ophthalmol

Evaluation of the effect of aging on retinal nerve fiber layer thickness measured by optical coherence tomography

Ophthalmologica

Relation of optic disc topography and age to thickness of retinal nerve fibre layer as measured using scanning laser polarimetry, in normal subjects

Br J Ophthalmol

Relation between size of optic disc and thickness of retinal nerve fibre layer in normal subjects

Br J Ophthalmol

Retinal nerve fibre layer thickness measurements in normal Indian population by optical coherence tomography

Indian J Ophthalmol

Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using StratusOCT

Invest Ophthalmol Vis Sci

Reproducibility of peripapillary retinal nerve fiber thickness measurements with Stratus OCT in glaucomatous eyes

Ophthalmology

Reproducibility of retinal nerve fiber thickness measurements using the Stratus OCT in normal and glaucomatous eyes

Invest Ophthalmol Vis Sci

Longitudinal variability of optic disc and retinal nerve fiber layer measurements

Invest Ophthalmol Vis Sci

Original article
Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: A Prospective Analysis of Age-Related Loss