Additional Guidance on the Use of the PRESERFLO™ MicroShunt in the Treatment of Glaucoma: Insights from a Second Delphi Consensus Panel.

INTRODUCTION: The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe. METHODS: Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel. A targeted literature review and expert steering committee guided Round 1 questionnaire development. Consensus was pre-defined at a threshold of ≥ 70% of panellists selecting 'strongly agree'/'agree' or 'strongly disagree'/'disagree' for 6-point Likert scale questions or ≥ 70% selecting the same option for multiple or single-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. RESULTS: In total, 28% (n = 9/32), 52% (n = 16/31) and 91% (n = 10/11) of statements reached consensus in Rounds 1, 2 and 3, respectively. There was agreement that the PMS may be used in patients with pigmentary, post-trauma or post-vitrectomy glaucoma and for patients with uveitic glaucoma without active inflammation. The PMS may be more suitable for patients with contact lenses than other subconjunctival filtering surgeries, without eliminating bleb-associated risks. Consensus was reached that combining PMS implantation and phacoemulsification may be as safe as standalone PMS surgery, but further efficacy data are required. Following a late rise in IOP ≥ 4 months post-surgery, topical aqueous suppressant drops or bleb revision may be suitable management options. CONCLUSIONS: This Delphi panel builds on the considerations explored in the 2021 Delphi panel and provides further detailed guidance for glaucoma surgeons on the use of the PMS, reflecting the availability of novel evidence and surgical experience. Videos are available for this article.

PRESERFLO™ Microshunt: 1-Year Results of a 25-Gauge vs. 27-Gauge Needle Tract.

Background: The purpose of this study was to evaluate the effectiveness and safety of the PreserFlo™ microshunt (PMS) using a 25-Gauge vs. 27-Gauge needle tract. Methods: This is a prospective postoperative examination of 60 glaucoma eyes that received a PMS. The main outcome measures were intraocular pressure (IOP), glaucoma drug score (GDS), Kaplan-Meier success rates, complications, and secondary intervention rates. Two subgroups were formed for data comparison: 27-Gauge (27G), and 25-Gauge (25G). Success was defined as IOP < 18 mmHg together with ≥20% IOP reduction with medication allowed (qualified success = QS18) or not (full success = FS18). Results: IOP and GDS were reduced from baseline to the 1-year study visit as follows: All eyes from 23.4 ± 8.6 mmHg (3.1 ± 0.9) to 15.1 ± 5.9 mmHg (0.8 ± 1.1); 25G from 24.2 ± 7.3 mmHg (3.0 ± 0.8) to 12.7 ± 2.7 mmHg (0.5 ± 0.8); and 27G from 23.1 ± 9.2 mmHg (3.1 ± 1.0) to 16.2 ± 6.7 mmHg (0.9 ± 1.2). IOP at one year was lower in the 25G group compared to the 27G group (p = 0.035). Bleb needling was required in eight (13.3%) eyes and open bleb revisions in three (5.0%). Transient hypotony occurred in 21% and choroidal effusion in 8% of all eyes. Choroidal effusions were more frequent in the 25G group (21%) compared to the 27G group (2%, p = 0.031). One-year success rates were significantly higher in the 25G group compared to the 27G group for both QS18 (25G: 67.9% vs. 27G: 35.7%, p = 0.002) and FS18 (25G: 63.6% vs. 27G: 29.2%, p = 0.007). Conclusions: The PreserFlo microshunt is an effective and safe glaucoma surgery with a low rate of bleb revisions or needlings. We show that the 25G needle tract might be more efficient for IOP control at the cost of increased IOP-related complications compared to 27G.

Characteristics of Henle's fiber layer in healthy and glaucoma eyes assessed by polarization-sensitive optical coherence tomography.

Using conventional optical coherence tomography (OCT), it is difficult to image Henle fibers (HF) due to their low backscattering potential. However, fibrous structures exhibit form birefringence, which can be exploited to visualize the presence of HF by polarization-sensitive (PS) OCT. We found a slight asymmetry in the retardation pattern of HF in the fovea region that can be associated with the asymmetric decrease of cone density with eccentricity from the fovea. We introduce a new measure based on a PS-OCT assessment of optic axis orientation to estimate the presence of HF at various eccentricities from the fovea in a large cohort of 150 healthy subjects. By comparing a healthy age-matched sub-group (N = 87) to a cohort of 64 early-stage glaucoma patients, we found no significant difference in HF extension but a slightly decreased retardation at about 2° to 7.5° eccentricity from the fovea in the glaucoma patients. This potentially indicates that glaucoma affects this neuronal tissue at an early state.

Thermally tuned VCSEL at 850†nm as a low-cost alternative source for full-eye SS-OCT.

Swept-source optical coherence tomography (SS-OCT) demonstrates superior performance in comparison to spectral domain OCT with regard to depth ranging. The main driver of cost for SS-OCT systems is, however, the price of the source. Here we show a low-cost alternative swept source that uses a thermally tuned vertical-cavity surface-emitting laser (VCSEL) at 850 nm. Its center wavelength can be tuned by adjusting the operating temperature through modulation of the injection current. At 2 kHz sweep rate, the depth range of the system was 5 cm, with a sensitivity roll-off of under -3 dB across this range. The system achieved a sensitivity of 97 dB with a sample beam power of 0.3 mW and an axial resolution of 50 µm in air. To demonstrate the system performance in vivo, an eye of a healthy volunteer was measured, and full-eye scans were acquired at 25 and 50 kHz from the cornea to the retina. Based on our results, we believe that this technology can be used as a cost-effective alternative OCT for point-of-care diagnostics.

Assessing the external validity of machine learning-based detection of glaucoma.

Studies using machine learning (ML) approaches have reported high diagnostic accuracies for glaucoma detection. However, none assessed model performance across ethnicities. The aim of the study is to externally validate ML models for glaucoma detection from optical coherence tomography (OCT) data. We performed a prospective, cross-sectional study, where 514 Asians (257 glaucoma/257 controls) were enrolled to construct ML models for glaucoma detection, which was then tested on 356 Asians (183 glaucoma/173 controls) and 138 Caucasians (57 glaucoma/81 controls). We used the retinal nerve fibre layer (RNFL) thickness values produced by the compensation model, which is a multiple regression model fitted on healthy subjects that corrects the RNFL profile for anatomical factors and the original OCT data (measured) to build two classifiers, respectively. Both the ML models (area under the receiver operating [AUC] = 0.96 and accuracy = 92%) outperformed the measured data (AUC = 0.93; P < 0.001) for glaucoma detection in the Asian dataset. However, in the Caucasian dataset, the ML model trained with compensated data (AUC = 0.93 and accuracy = 84%) outperformed the ML model trained with original data (AUC = 0.83 and accuracy = 79%; P < 0.001) and measured data (AUC = 0.82; P < 0.001) for glaucoma detection. The performance with the ML model trained on measured data showed poor reproducibility across different datasets, whereas the performance of the compensated data was maintained. Care must be taken when ML models are applied to patient cohorts of different ethnicities.

Quantitative assessment of depolarization by the retinal pigment epithelium in healthy and glaucoma subjects measured over a large field of view.

We present measurements of depolarization introduced by the retinal pigment epithelium (RPE) over a 45° field of view using polarization sensitive optical coherence tomography. A detailed spatial distribution analysis of depolarization caused by the RPE is presented in a total of 153 subjects including both healthy and diseased eyes. Age and sex related differences in the depolarizing character of the RPE are investigated.

Birefringent Properties of the Peripapillary Retinal Nerve Fiber Layer in Healthy and Glaucoma Subjects Analyzed by Polarization-Sensitive OCT.

Purpose: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT). Methods: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T. Results: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomatous eyes showed a statistically significant lower BIR globally (mean ± SD: 0.108 ± 0.008°/µm vs. 0.112 ± 0.009°/µm, P = 0.033), superiorly (0.116 ± 0.017°/µm vs. 0.126 ± 0.013°/µm, P = 0.0001), and inferiorly (0.112 ± 0.011°/µm vs. 0.121 ± 0.011°/µm, P < 0.0001), and increased BIR in the temporal quadrant (0.088 ± 0.015°/µm vs. 0.078 ± 0.014°/µm, P = 0.0001) compared to healthy eyes. Conclusions: We report a reduced BIR of the RNFL in early perimetric glaucoma, which can be interpreted as a sign of loss or change of intracellular microtubules and may contribute to a better understanding of early disease development. Prospective longitudinal studies are needed to determine whether BIR is altered in pre-perimetric human glaucoma before RNFL-T decline.

Retinal Oxygen Extraction in Patients with Primary Open-Angle Glaucoma.

Objective: To compare total retinal oxygen extraction between patients with primary open-angle glaucoma (POAG) and healthy control subjects. Design: A prospective, single-center, cross-sectional, case−control study performed at the Medical University of Vienna. Subjects: Forty patients with POAG and 40 age- and sex-matched control subjects. Methods: Total retinal blood flow was measured using Doppler optical coherence tomography (OCT). Retinal arterial and venous oxygen saturation was measured using reflectance spectroscopy. From these parameters, oxygen content in the retinal arterial and venous circulation as well as total retinal oxygen extraction were calculated. Results: Total retinal blood flow was lower in POAG (25.2 ± 6.7 µL/min) as compared to healthy control subjects (35.6 ± 8.3 µL/min, p < 0.001). Retinal arterial oxygen content was not different between the two groups (0.18 ± 0.01 mL(O2)/mL in both groups, p < 0.761), but retinal venous oxygen content was higher in POAG (0.15 ± 0.01 mL(O2)/mL) than in healthy controls (0.14 ± 0.01 mL(O2)/mL p < 0.001). Accordingly, retinal oxygen extraction was reduced in POAG (0.8 ± 0.3 µL(O2)/min as compared to healthy controls: 1.4 ± 0.4 µL(O2)/min, p < 0.001). There was a significant association between total retinal blood flow and total retinal oxygen extraction with measures of structural and functional damage (p < 0.001 each). Conclusions: This study indicates that POAG is associated with a reduction in total retinal oxygen extraction linked to structural and functional damage of the disease. Since the technology is non-invasive, it allows for longitudinal studies investigating to which degree low retinal oxygen extraction is linked to the progression of the disease.

Expert Consensus on the Use of the PRESERFLO™ MicroShunt Device in the Treatment of Glaucoma: A Modified Delphi Panel.

INTRODUCTION: The implantation of the PRESERFLO™ MicroShunt (PMS) device has been shown to significantly lower increased intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG). However, guidelines on best practice for patient selection and pre-/peri-/postoperative care management are lacking. The aim of this modified Delphi panel was to achieve expert consensus on the role of the PMS to treat patients with glaucoma in Europe. METHODS: Twelve European glaucoma surgeons experienced with the PMS procedure participated in a three-round modified Delphi panel. A targeted literature review and expert steering committee guided round 1 questionnaire development. Consensus was set at a pre-defined threshold of at least 70% of panellists selecting 'Strongly disagree'/'Disagree' or 'Strongly agree'/'Agree' for six-point Likert scale questions, or at least 70% selecting the same option for multiple-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. RESULTS: Consensus was achieved for 60.3% (n = 38/63), 60.0% (n = 18/30), and 100.0% (n = 11/11) of Likert/multiple-choice questions in rounds 1, 2, and 3, respectively. There was agreement that the PMS procedure is effective at reducing IOP in patients with high-tension POAG (greater than 21 mmHg). Although surgical techniques may vary slightly, consensus was reached on several points, including the importance of posterior application of mitomycin C (MMC). Panellists agreed that the PMS postoperative follow-up appointment schedule is reasonably predictable and mostly characterised by fewer visits than with trabeculectomy, particularly in the early phase. Although panellists agreed that combined cataract/PMS surgery and the use of non-MMC wound-healing modulators/antifibrotics during the procedure are possible, further data are needed to determine efficacy. CONCLUSION: The expert consensus reached in this panel will help inform best practice guidelines in the treatment of patients with glaucoma in Europe. Panellists also highlighted key areas for future research to improve understanding of the PMS in the treatment algorithm of glaucoma.

A multi-regression approach to improve optical coherence tomography diagnostic accuracy in multiple sclerosis patients without previous optic neuritis.

BACKGROUND: Optical coherence tomography (OCT) is a retinal imaging system that may improve the diagnosis of multiple sclerosis (MS) persons, but the evidence is currently equivocal. To assess whether compensating the peripapillary retinal nerve fiber layer (pRNFL) thickness for ocular anatomical features as well as the combination with macular layers can improve the capability of OCT in differentiating non-optic neuritis eyes of relapsing-remitting MS patients from healthy controls. METHODS: 74 MS participants (n = 129 eyes) and 84 age- and sex-matched healthy controls (n = 149 eyes) were enrolled. Macular ganglion cell complex (mGCC) thickness was extracted and pRNFL measurement was compensated for ocular anatomical factors. Thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between groups. RESULTS: Participants with MS showed significantly thinner mGCC, measured and compensated pRNFL (p ≤ 0.026). Compensated pRNFL achieved better performance than measured pRNFL for MS differentiation (AUC, 0.75 vs 0.80; p = 0.020). Combining macular and compensated pRNFL parameters provided the best discrimination of MS (AUC = 0.85 vs 0.75; p < 0.001), translating to an average improvement in sensitivity of 24 percent for differentiation of MS individuals. CONCLUSION: The capability of OCT in MS differentiation is made more robust by accounting OCT scans for individual anatomical differences and incorporating information from both optic disc and macular regions, representing markers of axonal damage and neuronal injury, respectively.

A multi-regression framework to improve diagnostic ability of optical coherence tomography retinal biomarkers to discriminate mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We assessed whether compensating the circumpapillary retinal nerve fiber layer (cpRNFL) thickness for multiple demographic and anatomical factors as well as the combination of macular layers improves the detection of MCI and AD. METHODS: This cross-sectional study of 62 AD (n = 92 eyes), 108 MCI (n = 158 eyes), and 55 cognitively normal control (n = 86 eyes) participants. Macular ganglion cell complex (mGCC) thickness was extracted. Circumpapillary retinal nerve fiber layer (cpRNFL) measurement was compensated for several ocular factors. Thickness measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between the groups. The main outcome measure was OCT thickness measurements. RESULTS: Participants with MCI/AD showed significantly thinner measured and compensated cpRNFL, mGCC, and altered retinal vessel density (p < 0.05). Compensated RNFL outperformed measured RNFL for discrimination of MCI/AD (AUC = 0.74 vs 0.69; p = 0.026). Combining macular and compensated cpRNFL parameters provided the best detection of MCI/AD (AUC = 0.80 vs 0.69; p < 0.001). CONCLUSIONS AND RELEVANCE: Accounting for interindividual variations of ocular anatomical features in cpRNFL measurements and incorporating macular information may improve the identification of high-risk individuals with early cognitive impairment.

Automatic retinal nerve fiber bundle tracing based on large field of view polarization sensitive OCT data.

A technique to accurately estimate trajectories of retinal nerve fiber bundles (RNFB) in a large field of view (FOV) image covering 45° is described. The method utilizes stitched projections of polarization-sensitive optical coherence tomography (PS-OCT) data, as well as a mathematical model of average RNFB trajectories as prior. The fully automatic process was applied to data recorded in healthy subjects and glaucoma patients and automatically detected individual RNFB trajectories are compared to manual traces.

Optical coherence tomography-measured retinal nerve fiber layer thickness values compensated with a multivariate model and discrimination between stable and progressing glaucoma suspects.

PURPOSE: Our previously introduced multivariate model, compensating for intersubject variability, was applied to circumpapillary retinal nerve fiber layer (RNFL) values measured with optical coherence tomography in glaucoma suspects with or without prior progressive optic disc (OD) change in a series of confocal scanning laser tomography (CSLT, HRT III) measurements. METHODS: In this prospective study, OD change during CSLT follow-up was determined with strict, moderate, and liberal criteria of the topographic change analysis (TCA). Model compensation (MC) as well as age compensation (AC) was applied to RNFL sectors (RNFLMC vs. RNFLAC). Diagnostic performance of RNFLMC vs. RNFLAC was tested with an area under the receiver operating characteristic (AUROC) and was compared between methods. RESULTS: Forty-two glaucoma suspects were included. Patients without prior progressive OD change during the CSLT follow-up (= stable) had thicker RNFL thickness values in most areas and for all progression criteria. RNFLMC AUROC for the global RNFL (0.719) and the inferior quadrant (0.711) performed significantly better compared with RNFLAC AUROC (0.594 and 0.631) to discriminate between stable and progressive glaucoma suspects as defined by the moderate criteria of CSLT progression analysis (p = 0.028; p = 0.024). CONCLUSION: MC showed a slight but significant improvement in detection of subjects with prior progressive OD change among a group of glaucoma suspects, when compared to AC, which is the compensation method commonly used during OCT data evaluation in daily routine. Further studies are warranted to validate the present results.

Multivariate Normative Comparison, a Novel Method for Improved Use of Retinal Nerve Fiber Layer Thickness to Detect Early Glaucoma.

PURPOSE: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred eighty-seven patients with glaucoma and 2699 healthy participants. METHODS: Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. MAIN OUTCOME AND MEASURES: Measured and compensated RNFL thickness measurements. RESULTS: After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001). CONCLUSIONS: The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection.

Temporal phase evolution OCT for measurement of tissue deformation in the human retina in-vivo.

We demonstrate the use of temporal phase evolution (TPE-) OCT methods to evaluate retinal tissue deformation in-vivo over time periods of several seconds. A custom built spectral domain (SD)-OCT system with an integrated retinal tracker, ensuring stable imaging with sub-speckle precision, was used for imaging. TPE-OCT measures and images phase differences between an initial reference B-scan and each of the subsequent B-scans of the evaluated temporal sequence. In order to demonstrate the precision and repeatability of the measurements, retinal nerve fiber (RNF) tissue deformations induced by retinal vessels pulsating with the heartbeat were analyzed in several healthy subjects. We show TPE maps (M-scans of phase evolution as a function of position along B-scan trace vs. time) of wrapped phase data and corresponding deformation maps in selected regions of the RNF layer (RNFL) over the course of several cardiac cycles. A reproducible phase pattern is seen at each heartbeat cycle for all imaged volunteers. RNF tissue deformations near arteries and veins up to ∼ 1.6 µm were obtained with an average precision for a single pixel of about 30 nm. Differences of motion induced by arteries and veins are also investigated.

Needling and open filtering bleb revision after XEN-45 implantation-a retrospective outcome comparison.

PURPOSE: To compare efficacy and safety of needling and open bleb revision after XEN-45 surgery. METHODS: This retrospective study represents real-life data of patients who underwent XEN-45 surgery between November 2014 and June 2018 in the Vienna General Hospital. The following groups were formed for data evaluation: (PSEA) primary surgery secondary intervention allowed (n = 268); (PS) primary surgery until secondary intervention (n = 268); (N) first needling until additional secondary intervention (n = 55); (BR) first bleb revision until additional secondary intervention (n = 105). Main outcome measures were pre- and postoperative intraocular pressure (IOP), number of glaucoma medication (GM), Kaplan-Meier success rates, and secondary intervention rates. Success was defined as postoperative IOP < 21 mmHg and < 18 mmHg together with ≥ 20% IOP reduction with medication allowed. RESULTS: IOP (and GM) was lowered from 23.5 ± 8.0 (GM 3.1 ± 1.0) to 14.9 ± 8.2 mmHg (1.2 ± 1.4) in group PSEA and 18.1 ± 8.2 mmHg (1.5 ± 1.4) in group PS, in group N from 23.2 ± 10.1 (1.5 ± 1.0) to 19.3 ± 8.5 mmHg (2.2 ± 1.3) and in group BR from 22.0 ± 8.0 mmHg (2.5 ± 1.1) to 15.5 ± 6.4 mmHg (1.3 ± 1.5) after a median follow-up of 16.0, 8.4, 4.8, and 7.3 months, respectively. Success rates at 1 year were significantly higher in group BR (50.7%) compared to PS (37.7%, p = 0.019) and N (24.3%; p = 0.015). An additional intervention was required less frequently in group BR (17.1%) compared to group PS (49.6%, p < 0.001) and group N (54.5%, p < 0.001). CONCLUSION: Our data appear to indicate favorable outcomes for open XEN bleb revision in terms of Kaplan-Meier success rates and secondary intervention rate compared to the needling procedure.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

Purpose: To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT). Methods: In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC). Results: Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group. Conclusions: We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

Analysis of retinal nerve fiber layer birefringence in patients with glaucoma and diabetic retinopathy by polarization sensitive OCT.

The retinal nerve fiber layer (RNFL) is a fibrous tissue that shows form birefringence. This optical tissue property is related to the microstructure of the nerve fiber axons that carry electrical signals from the retina to the brain. Ocular diseases that are known to cause neurologic changes, like glaucoma or diabetic retinopathy (DR), might alter the birefringence of the RNFL, which could be used for diagnostic purposes. In this pilot study, we used a state-of-the-art polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker to analyze the RNFL birefringence in patients with glaucoma, DR, and in age-matched healthy controls. We recorded 3D PS-OCT raster scans of the optic nerve head area and high-quality averaged circumpapillary PS-OCT scans, from which RNFL thickness, retardation and birefringence were derived. The precision of birefringence measurements was 0.005°/µm. As compared to healthy controls, glaucoma patients showed a slightly reduced birefringence (0.129 vs. 0.135°/µm), although not statistically significant. The DR patients, however, showed a stronger reduction of RNFL birefringence (0.103 vs. 0.135°/µm) which was highly significant. This result might open new avenues into early diagnosis of DR and related neurologic changes.

Diagnostic Ability of Individual Macular Layers by Spectral-Domain OCT in Different Stages of Glaucoma.

PURPOSE: To compare the diagnostic ability of macular intraretinal layer thickness with circumpapillary retinal nerve fiber layer (cpRNFL) thickness, either when used individually or in combination with cpRNFL for detecting early, moderate, and advanced glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 423 glaucoma participants and 423 age- and gender-matched normal participants. METHODS: Participants underwent Cirrus spectral-domain OCT (SD-OCT) imaging (Carl Zeiss Meditec, Dublin, CA) using the optic disc and macular scanning protocols. Iowa Reference Algorithms (version 3.8.0) were used for intraretinal layer segmentation, and mean thickness of intraretinal layers was rescaled with magnification correction using axial length value. Thickness measurements of each layer/sector and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Glaucoma eyes were subdivided based on of their visual field severity (early, n = 234; moderate, n = 107; advanced, n = 82). MAIN OUTCOME MEASURES: Intraretinal layers. RESULTS: Some 67% of participants were male, their average ± standard deviation age was 65±9 years. Circumpapillary retinal nerve fiber layer, macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) were significantly thinner in the glaucoma groups (P < 0.0005). The 2 best parameters for detecting normal eyes from early glaucoma was cpRNFL (AUC = 0.861) and mGCL (AUC = 0.842), from moderate glaucoma was mGCL combined with inner plexiform layer (IPL) (AUC = 0.915) and cpRNFL (AUC = 0 .914), and from advanced glaucoma was mGCL-IPL (AUC = 0.984) and cpRNFL (AUC = 0.977). There was no statistical significance between AUCs for the macular parameter and cpRNFL thickness measurement at any of the severities (P > 0.05). Combining macular and cpRNFL parameters improved the diagnostic performance for early glaucoma (AUC = 0.908; P = 0.002) and moderate glaucoma (AUC = 0.944; P = 0.031) but not for advanced glaucoma (AUC = 0.991; P > 0.05). CONCLUSIONS: Single-layer mGCL thickness is comparable to the traditional cpRNFL thickness for the diagnosis of early/moderate glaucoma, whereas cpRNFL thickness remains the most efficient for advanced glaucoma. Combining macular measurements (GCL and GCL-IPL) and cpRNFL improved the discrimination of early/moderate glaucoma but not of advanced glaucoma. For the diagnosis of early glaucoma, both macular and optic disc scans should be used.