Retinal Nerve Fiber Layer Thickness Loss Research Articles

Basal Blood Flow and Autoregulation Changes in the Optic Nerve of Rhesus Monkeys with Idiopathic Bilateral Optic Atrophy

To characterize the hemodynamic features and the association with structural damage in the optic nerve head (ONH) of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys. In five animals with BOA and nine healthy animals under general anesthesia (pentobarbital), intraocular pressure (IOP) was manometrically controlled. ONH blood flow was measured with a laser speckle flow graph device. Basal blood flow in global and quadrantal sectors was measured with IOP set at 10 mm Hg; autoregulation capacity was assessed by comparing blood flow changes before and after IOP was increased from 10 to 30 mm Hg. Spectral-domain optic coherence tomography was used to measure retinal nerve fiber layer thickness (RNFLT) by peripapillary circular scans. Compared with control eyes, RNFLT in BOA eyes was significantly less in all sectors (P < 0.001) except the nasal (P = 0.25); the average global and sectoral blood flow in all quadrants was significantly lower (P < 0.001). These blood flow changes were significantly correlated with corresponding sectoral RNFLT (P < 0.01) except the nasal (P = 0.25). After IOP was increased to 30 mm Hg, global blood flow was significantly reduced (P < 0.001), but with no regional preferences despite prominent temporal RNFLT loss; no significant blood flow change was observed in control eyes (P = 0.24). Basal blood flow and autoregulation capacity in the ONH of BOA were significantly compromised, with a close correlation to structural changes. The hemodynamic changes showed no regional preference across the ONH, which was consistent with postmortem histological observations.

THE LONGITUDINAL CHANGES OF RETINAL NERVE FIBER LAYER THICKNESS AFTER PANRETINAL PHOTOCOAGULATION IN DIABETIC RETINOPATHY PATIENTS

To investigate longitudinal changes in retinal nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) in diabetic retinopathy patients. This prospective study examined 31 eyes in 25 patients undergoing PRP, who were diagnosed with severe nonproliferative diabetic retinopathy or non-high-risk proliferative diabetic retinopathy. Optical coherence tomography was conducted before PRP and at 3, 6, 12, and 24 months after PRP to investigate changes in peripapillary RNFL thickness. Superior, nasal, inferior, temporal, and mean peripapillary RNFL thickness increased until 6 months after PRP and then decreased. Superior RNFL thickness increased significantly at 3 and 6 months and decreased significantly at 24 months compared with the baseline RNFL thickness. Nasal RNFL thickness declined significantly at 24 months compared with the baseline RNFL thickness without any significant increase in thickness during the follow-up period. Inferior RNFL thickness increased significantly at 6 months and decreased significantly at 24 months compared with its baseline RNFL thickness. Temporal thickness increased significantly at 3, 6, 12, and 24 months compared with the baseline RNFL thickness. Mean RNFL thickness increased significantly at 6 months and decreased significantly at 24 months. Central subfield thickness increased significantly at 3, 6, 12, and 24 months compared with its baseline thickness. Peripapillary RNFL thickness increased at 6 months after PRP and then decreased at 24 months after PRP compared with baseline peripapillary RNFL thickness in diabetic retinopathy patients. This finding suggests that in addition to diabetes itself, diabetic retinopathy, and associated glaucoma, PRP may be a cause of RNFL thickness loss in patients with diabetes.

Relationship between Orbital Optic Nerve Axon Counts and Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography

We determined the relationship between total optic nerve axon counts and peripapillary retinal nerve fiber layer thickness (RNFLT) measured in vivo by spectral domain optical coherence tomography (SDOCT). A total of 22 rhesus macaques had three or more baseline measurements in both eyes of peripapillary RNFLT made by SDOCT. Laser photocoagulation then was applied to the trabecular meshwork of one eye to induce chronic unilateral IOP elevation. SDOCT measurements of RNFLT continued approximately every two weeks until the predefined study endpoint was reached in each animal. At endpoint, animals were sacrificed and the optic nerve was sampled approximately 2 mm behind the globe to obtain thin sections for histologic processing and automated axon counting across 100% of the optic nerve cross-sectional area. At the final imaging session, the average loss of RNFLT was 20 ± 21%, ranging from essentially no loss to nearly 65% loss. Total optic nerve axon count in control eyes ranged from 812,478 to 1,280,474. The absolute number of optic nerve axons was related linearly to RNFLT (axon count = 12,336 × RNFLT((μm)) - 257,050, R(2) = 0.65, P < 0.0001), with a Pearson correlation coefficient of 0.81. There also was a strong linear relationship between relative optic nerve axon loss (glaucomatous-to-control eye) and relative RNFLT at the final imaging session, with a slope close to unity but a significantly negative intercept (relative axon loss((%)) = 1.05 × relative RNFLT loss((%)) - 14.4%, R(2) = 0.75, P < 0.0001). The negative intercept was robust to variations of fitted model because relative axon loss was -14% on average for all experimental glaucoma (EG) eyes within 6% (measurement noise) of zero relative loss. There is a strong linear relationship between total optic nerve axon count and RNFLT measured in vivo by SDOCT. However, substantial loss of optic nerve axons (∼10%-15%) exists before any loss of RNFLT manifests and this discrepancy persists systematically throughout a wide range of damage.

Decreased retinal sensitivity and loss of retinal nerve fibers in multiple system atrophy

In a previous study, retinal nerve fiber layer thickness (RNFLT) loss was shown as part of the neurodegenerative process in multiple system atrophy (MSA). Here, we investigate in a larger cohort of MSA patients whether the RNFLT loss translates into respective visual field defects. Spectral domain optical coherence tomography was performed in 20 MSA patients (parkinsonian subtype = 12, cerebellar subtype = 8) to quantify peripapillary RNFLT. Visual field (90°) was analyzed by automated static perimetry to investigate retinal structure/function relationship. Eight data sets did not meet stringent quality criteria, and only 12 data sets were further analyzed. Compared to healthy controls, MSA patients demonstrated a significant reduction of RNFLT in the nasal sectors (p ( nasal-superior ) = 0.02, p ( nasal ) = 0.03, p ( nasal-inferior ) < 0.01), while changes in temporal RNFLT measures (p ( temporal-superior ) = 0.42, p ( temporal ) = 0.34, p ( temporal-inferior ) = 0.25) were not statistically significant compared to healthy controls (ANOVA). MSA patients featured a significant global mean deviation (2.74 dB; p < 0.01) without predominant peripheral visual field defects. Statistical analysis of mean defect in the central (0-30°), peripheral (30-90°) or global (0-90°) visual field revealed no significant correlation (r (2) (central) = 0.11, r (2) (peripheral) = 0.04, r (2) (global) = 0.07) with nasal RNFLT in MSA patients. MSA patients feature significant reduction in nasal RNFLT and global mean deviation when compared to healthy controls, consistent with the multi-systemic nature of this neurodegenerative disorder. This finding provides first evidence for two independent deteriorations of the visual system in MSA.

The impact of brimonidine on the loss of retinal nerve fiber layer (RNFL) thickness in glaucoma diabetic patients

AbstractPurpose Brimonidine has proved protective effects on Retinal Ganglion Cells (in animal researches with intravitreal injection), but when used in topical application, its neuroprotective activity has not been unequivocally confirmed. A trail to evaluate potential neuroprotective effect of brimonidine on RNFL in Glaucoma patients.Methods After a retrospective analysis of 1800 patients data, we selected 98, who revealed a significant RNFL thickness loss (21 had Diabetes). We compared the rate of RFNL loss between the group of 53 patients (100 eyes) treated with brimonidine and 45 (90 eyes) treated with other drugs.Results In patients with well‐controlled intraocular pressure (IOP) there is statistically significant relationship between the use of brimonidine and loss of RNFL thickness (p &lt;0.01) and an annual rate of RNFL loss (p=0.01).Conclusion The potentially neuroprotective effect of brimonidine depends on IOP. The higher than normal IOP will limit this potential effect.

Retinal nerve fibre layer and visual function loss in glaucoma: the tipping point

AimsTo determine the retinal nerve fibre layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss.MethodsIn a prospective cross-sectional study, 72 healthy and 40...

Retinal nerve fiber layer defect patterns in primary angle-closure and open-angle glaucoma: A comparison using optical coherence tomography

To compare the patterns of retinal nerve fiber layer (RNFL) thickness loss in primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) using optical coherence tomography (OCT). Forty-three participants with PACG and 60 with POAG underwent fast RNFL thickness measurement by OCT. Eyes were classified according to the visual field mean deviation (VF-MD) into mild (>-8 dB), moderate (-8 dB to >-16 dB), and advanced (≤ -16 dB) glaucoma subgroups. The raw RNFL thickness data were compared with data from the Thai normative database. Mean (SD) age was 67.0 (9.6) and 64.1 (11.6) years in the PACG and POAG groups, respectively (P = 0.19). In the mild subgroups, a focal RNFL thickness loss was found in the inferior area in the POAG group, but not in the PACG group. The RNFL defect involved sectors 1, 6, and 7 in the moderately advanced disease subgroups of both PACG and POAG and extended through almost all sectors in the advanced disease subgroups. The deepest RNFL defect, -17.25 μm, was found in sector 6 of the mild POAG subgroup, compared with -8.78 μm in the PACG group (P = 0.04). The number of affected points in each sector in the mild subgroups was greater in the POAG group than in the PACG group. Participants with mild POAG had deeper and more localized RNFL defects than did participants with PACG. The pattern was similar in participants with moderate or advanced disease.

Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients

Objective Optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis (MS) research and has been suggested as outcome measure for neuroprotective therapies. However, to date it is not clear whether patterns of retinal nerve fiber layer thickness (RNFLT) loss are different in MS compared to other diseases such as glaucoma and data on RNFLT loss in MS patients with or without optic neuritis (ON/NON) have remained inconsistent or even contradictory. Methods In this large cross-sectional study we analyzed the patterns of axonal loss of retinal ganglion cells in MS eyes ( n = 262) with and without history of ON (MS/ON: 73 eyes; MS/NON: 189 eyes) and patients eyes with glaucomatous optic disc atrophy (GA: n = 22; 39 eyes) in comparison to healthy control eyes (HC: n = 406 eyes). Results We found that significant average and quadrant RNFLT loss is detectable by OCT in both MS and GA patients compared to healthy controls ( p < 0.01). The age- and gender adjusted average and quadrant RNFLT did not differ significantly between MS and GA patients ( p > 0.05). Average ( p < 0.0001) and quadrant ( p < 0.05) RNFL thinning is significantly more severe in MS/ON versus MS/NON eyes, and the extent of RNFL thinning varies across quadrants in MS/ON eyes with the highest degree of RNFLT loss in the temporal quadrant ( p < 0.001). Conclusion RNFLT reduction across all four quadrants in MS patients as a whole as well as in MS/NON eyes argues for a diffuse neurodegenerative process. Superimposed inflammatory attacks to the optic nerve may cause additional axonal damage with a temporal preponderance. Future studies are necessary to further evaluate the capacity of OCT to depict disease specific damage patterns.

Decreased Retinal Ganglion Cell Layer Thickness in Patients with Type 1 Diabetes

PURPOSE. To determine which retinal layers are most affected by diabetes and contribute to thinning of the inner retina and to investigate the relationship between retinal layer thickness (LT) and diabetes duration, diabetic retinopathy (DR) status, age, glycosylated hemoglobin (HbA1c), and the sex of the individual, in patients with type 1 diabetes who have no or minimal DR. METHODS. Mean LT was calculated for the individual retinal layers after automated segmentation of spectral domain-optical coherence tomography scans of patients with diabetes and compared with that in control subjects. Multiple linear regression analysis was used to determine the relationship between LT and HbA1c, age, sex, diabetes duration, and DR status. RESULTS. In patients with minimal DR, the mean ganglion cell layer (GCL) in the pericentral area was 5.1 mum thinner (95% confidence interval [CI], 1.1-9.1 mum), and in the peripheral macula, the mean retinal nerve fiber layer (RNFL) was 3.7 mum thinner (95% CI, 1.3-6.1 mum) than in the control subjects. There was a significant linear correlation (R = 0.53, P < 0.01) between GCL thickness and diabetes duration in the pooled group of patients. Multiple linear regression analysis (R = 0.62, P < 0.01) showed that DR status was the most important explanatory variable. CONCLUSIONS. This study demonstrates GCL thinning in the pericentral area and corresponding loss of RNFL thickness in the peripheral macula in patients with type 1 diabetes and no or minimal DR compared with control subjects. These results support the concept that diabetes has an early neurodegenerative effect on the retina, which occurs even though the vascular component of DR is minimal.

Quantifying Retinal Nerve Fiber Layer Loss in Glaucoma Using a Model of Unilateral Hypertensive Pseudoexfoliation Syndrome

To correlate the amount of glaucomatous field loss with amount of retinal nerve fiber layer (RNFL) loss using a novel model consisting of eyes of subjects with pseudoexfoliation syndrome (PXS) in 1 eye only with elevated intraocular pressure, using the fellow eye as a marker of baseline healthy anatomy, allowing precise correlation by elimination of intersubject anatomic variation. In each eye with PXS we recorded standard automated perimetry mean deviation and the percentage loss of Stratus optical coherence tomography - RNFL thickness relative to the fellow non-PXS eye, and correlated these 2 measurements. Twenty-six subjects with unilateral hypertensive PXS were enrolled. Twelve of 26 eyes had glaucomatous visual field loss. In eyes without field defect there was a broad range of RNFL thickness loss from almost none to nearly 50%. In some of these eyes whereas RNFL thickness was within normal limits it was clearly reduced compared with the fellow eye. All eyes with field defect except one had lost greater than 50% RNFL thickness. This model of unilateral hypertensive PXS allows correlation of functional and structural loss in glaucoma while eliminating interindividual anatomic variability. It suggests that optical coherence tomography can have an important role in the diagnosis and management of early glaucoma before visual field loss is detected.

Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies

To evaluate the retinal nerve fiber layer (RNFL) thickness and macular volume in neuromyelitis optica (NMO) spectrum patients using optical coherence tomography (OCT). OCT can quantify damage to retinal ganglion cell axons and can identify abnormalities in multiple sclerosis and optic neuritis (ON) eyes. OCT may also be useful in the evaluation of patients with NMO. OCT and visual function testing were performed in 26 NMO spectrum patients with a history of ON, 17 patients with isolated longitudinally extensive transverse myelitis (LETM) without ON, 378 patients with relapsing-remitting multiple sclerosis (RRMS), and 77 healthy controls at 2 centers. Substantial RNFL thinning was seen in NMO ON eyes (63.6 microm) relative to both RRMS ON eyes (88.3 microm, p < 0.0001) and control eyes (102.4 microm, p < 0.0001). A first episode of ON was estimated to cause 24 microm more loss of RNFL thickness in NMO than RRMS. Similar results were seen for macular volume. ON also was associated with more severe visual impairment in NMO spectrum patients than in RRMS patients. Eyes in the LETM group and unaffected NMO eyes were not significantly different from controls, though conclusions about these subgroups were limited by small sample sizes. Optical coherence tomography (OCT) shows more severe retinal damage after optic neuritis (ON) episodes in neuromyelitis optica (NMO) than in relapsing-remitting multiple sclerosis. Identification of substantial retinal nerve fiber layer loss (>15 microm) after ON in a non-multiple sclerosis patient should prompt consideration of an NMO spectrum condition. OCT may be a useful tool for the evaluation of patients with NMO.

The Relationship between Visual Field and Retinal Nerve Fiber Layer Measurements in Patients with Multiple Sclerosis

To investigate the relationship between visual function, measured by standard automated perimetry (SAP), and retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT), in patients with multiple sclerosis (MS). SAP and RNFL thickness were measured in patients with MS in 28 eyes with the last optic neuritis (ON) >or=6 months prior (ON group) and 33 eyes without ON history (non-ON group). Abnormal overall or quadrant RNFL thickness was defined by measured values below 5% of the norm. A whole visual field or a sector of the field was classified as abnormal by using cluster criteria on total-deviation plots. Agreement between SAP and OCT results in classifying eyes/sectors was presented as a percentage of observed agreement, along with the AC1 statistic, which corrects for chance agreement. Regression analyses were performed relating several SAP parameters and RNFL thickness in the ON group. ON eyes showed more loss of visual sensitivity (MD, P = 0.02) and more loss of RNFL thickness (P < 0.0001) than did non-ON eyes. SAP and OCT agreed in 86% (AC1 = 0.78) of eyes and 69% (AC1 = 0.38) of sectors in the ON group and 61% (AC1 = 0.33) of eyes and 66% (AC1 = 0.48) of sectors in the non-ON group. Overall RNFL thickness was related to MD (dB) by a simple exponential function (R(2) = 0.48), supporting a linear relationship between these measures when both are expressed on linear scales. Absolute Pearson correlation coefficients for overall RNFL thickness and several SAP parameters ranged from 0.51 to 0.69. Good agreement between SAP and OCT was found in ON eyes but not in non-ON eyes or in individual sectors in either group. The findings in this study provide further support for the utility of combining structural and functional testing in clinical research on patients with MS, as well as in future neuroprotection trials for which the anterior visual pathways in patients with MS and optic neuritis may be used as a model.

Optical Coherence Tomography and Histologic Measurements of Nerve Fiber Layer Thickness in Normal and Glaucomatous Monkey Eyes

To investigate optical coherence tomography (OCT) measurements of retinal nerve fiber layer (RNFL) thickness change associated with elevated intraocular pressure (IOP) over a period of time, and to compare in vivo OCT RNFL thickness measurements with morphologic measurements of the same tissues. One eye of each of 12 cynomolgus monkeys was treated with argon laser to the anterior chamber angle to induce elevated IOP. OCT measurements were made weekly in the treated and the contralateral eyes of each monkey for 14 weeks after the laser insult. The monkeys were killed at the conclusion of the experiment, and comparisons were made between the terminal OCT RNFL measurements and quantitative histomorphometric assessments in the same eyes. Effects of exposure to elevated IOP on RNFL were characterized by a mixed-effects model. Linear mixed-effects models provided unbiased analysis of balanced and unbalanced repeated-measures data, detection of group effects (fixed effects), and individual subject effects (random effects), thereby making the best use of all available data. Increased IOP was achieved in 10 eyes. Exposure to high IOP was associated with the loss of mean RNFL thickness at a median rate of 3.77 +/- 0.08 microm/wk. On average, OCT RNFL thickness measurements were higher than histomorphologic measurements by 5.7 microm (95% confidence interval, 3.6-7.8; P = 0.003). Thinning of the RNFL associated with elevated IOP was demonstrated with OCT in a group of experimentally glaucomatous monkey eyes over a period. OCT measurements corresponded with histomorphometric measurements of the same tissues.

Laser Scanning Confocal Ophthalmoscopy and Polarimetry of Human Immunodeficiency Virus Patients Without Retinopathy, Under Antiretroviral Therapy

Confocal laser scanning ophthalmoscopy (HRT; Heidelberg retinal tomograph II) and scanning laser polarimetry (GDx-variable corneal compensator [VCC]) were used to investigate whether early indicators of retinal nerve fiber layer (RNFL) thickness loss could be observed in patients infected with the human immunodeficiency virus (HIV) that had no associated retinopathy or optic neuropathy and were concomitantly receiving antiretroviral medications. HRT and GDx-VCC parameters obtained from a group of 13 HIV-positive subjects (n=26 eyes) on antiretroviral therapy examined with HRT, with a subgroup of six subjects (n=12 eyes) examined with both HRT and GDx-VCC, were compared with those of a matched HIV-negative control cohort (13 subjects, n=26 eyes) examined with HRT, with a subgroup of five subjects (n=10 eyes) examined with both HRT and GDx-VCC. We employed generalized estimating equations for statistical analysis. Reduced mean values for the HRT height variation contour (p<0.045) and HRT mean RNFL thickness (p<0.023) were observed in HIV-positive subjects controlling for age, sex, and race. A significantly reduced mean value corresponding to the GDx-VCC superior maximum (p<0.014) and inferior maximum (p<0.016) were also observed for the HIV-positive cohort analyzed controlling for age, sex, and race. HRT and GDx-VCC indicators of RNFL thickness appear to be significantly reduced in HIV-positive subjects without retinopathy or optic nerve disease using antiretroviral medication, suggesting RNFL loss occurs in this population of HIV-positive patients. The lack of correlation between CD4 counts, viral load, number of antiretroviral medications used, or years from diagnosis of HIV and RNFL thinning, suggests that possibly other factors associated with HIV infection may contribute to the apparent RNFL thickness loss.

Retinal nerve fiber layer thinning in Parkinson disease

Retinal dopamine loss in Parkinson disease (PD) is reflected by visual neurophysiological dysfunction. We measured the thickness of the circumpapillary retinal nerve fiber layer (RNFL) in PD patients using optical coherence tomography. The thickness in the inferior quadrant of PD patients (147 ± 20 microns) was significantly thinner than that of controls (173 ± 12 microns; p = 0.002), while the inferotemporal area was the thinnest (146 ± 24 vs. 191 ± 21 microns; p = 0.0003). The results show significant loss of RNFL thickness in PD at specific sites.