Publications by authors named "Robert N Weinreb"

720 Publications

Association of visual field pattern reversal with paracentral visual field loss.

Ophthalmol Glaucoma 2021 Oct 21. Epub 2021 Oct 21.

Hamilton Glaucoma Center, Shiley Eye Institute, and Viterbi Family Department of Ophthalmology, University of California San Diego.

Purpose: Visual fields (VFs) that have more test points outside normal limits on the pattern deviation map than on the total deviation map have been assumed to be evidence of an unreliable VF. We propose the term "pattern reversal" to describe this VF finding and explore its association with paracentral loss.

Design: Retrospective cohort and case-control studies.

Subjects: Glaucoma and glaucoma suspect patients that completed VF testing in Veteran's Affairs ophthalmology or optometry clinics.

Methods: In the cohort study VFs were included that demonstrated pattern reversal. The area of pattern reversal was categorized as peripheral, paracentral, or mixed (both peripheral and paracentral). In the case-control study, a group of patients with paracentral loss confirmed on 10-2 VFs were compared to a control group of VFs without paracentral loss.

Main Outcome Measures: In the cohort study the calculated false positive (FP) error rates were compared among groups categorized by area of pattern reversal. In the case-control study the rates of pattern reversal were compared between patients with and without paracentral loss.

Results: 217 eyes of 145 patients were included in the cohort study. VFs with pattern reversal and mixed loss had significantly higher FP rates compared to those with paracentral or peripheral loss only (16.25% vs 6.26% and 8.15%, respectively, p<0.001). 55 eyes of 41 patients were included in the case group and 55 eyes of 41 patients were included in the control group. Patients with paracentral loss were more likely to have history of pattern reversal compared to those without paracentral loss (58.2% vs 29.1%, p=0.004). Twelve eyes with paracentral loss had 24-2 VFs that showed defects on the pattern deviation map but not on the total deviation map CONCLUSIONS: Pattern reversal may be associated with paracentral VF loss and is not always associated with elevated FP rates.
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http://dx.doi.org/10.1016/j.ogla.2021.10.009DOI Listing
October 2021

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in the Human Eye.

Ocul Immunol Inflamm 2021 Oct 12:1-7. Epub 2021 Oct 12.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, California, USA.

Purpose: To determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in postmortem ocular specimens of patients with severe COVID-19 disease.

Patients And Methods: Postmortem conjunctival (28 samples), aqueous humor (30 samples) and vitreous humor (30 samples) specimens were obtained bilaterally from the eyes of 15 deceased COVID-19 patients within one hour of death. The presence of viral RNA was evaluated in samples using Real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Positive RT-PCR SARS-COV-2 results were found in one conjunctival and 2 vitreous humor samples. All aqueous humor samples tested negative for the presence of SARS-COV-2 RNA. Of note, three positive samples were obtained from three different patients. The overall prevalence of positive RT-PCR ocular samples was 3.4% among all samples and 20% at the patient level.

Conclusion: SARS-CoV-2 RNA is detectable in postmortem conjunctival and vitreous humor samples of patients with severe COVID-19.
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http://dx.doi.org/10.1080/09273948.2021.1980810DOI Listing
October 2021

Measurements of OCTA Complement OCT for Diagnosing Early Primary Open Angle Glaucoma.

Ophthalmol Glaucoma 2021 Oct 8. Epub 2021 Oct 8.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA. Electronic address:

Purpose: To compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness, and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).

Design: Cross-sectional study PARTICIPANTS: Eighty healthy eyes, 64 pre-perimetric, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.

Methods: Global and regional RNFL thickness and cpCD measurements were obtained using optical coherence tomography (OCT) and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.

Main Outcome Measures: RNFL thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect pre-perimetric glaucoma and glaucoma. R-squared for the strength of associations between RNFL thickness-function and capillary density-function in diagnostic groups.

Results: Both global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P<0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P<0.05) in pre-perimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, IOP and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P<0.05). Global measurements of capillary density (whole image capillary density [wiCD] and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting pre-perimetric glaucoma and glaucoma (P<0.05; except for cpCD/RNFL thickness comparison in glaucoma [P=0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P<0.05, except for temporal RNFL thickness-function association [P=0.070]).

Conclusions: Associations between capillary density and visual function were found in the regions known to be at highest risk for damage in pre-perimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared to RNFL thickness loss. RNFL thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.
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http://dx.doi.org/10.1016/j.ogla.2021.09.012DOI Listing
October 2021

Reply.

Ophthalmology 2021 Oct 5. Epub 2021 Oct 5.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, UC San Diego, La Jolla, California. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2021.08.022DOI Listing
October 2021

Response to Letter to the Editor: Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect and Glaucoma Eyes.

J Glaucoma 2021 Oct 11. Epub 2021 Oct 11.

Hamilton Glaucoma Center, Shiley Eye Institute, and the Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, United States.

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http://dx.doi.org/10.1097/IJG.0000000000001951DOI Listing
October 2021

A Modified Technique in Applying Sponge Soaked with Mitomycin C in Trabeculectomy.

Asia Pac J Ophthalmol (Phila) 2021 Sep 26. Epub 2021 Sep 26.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China Bernard and Shirlee Brown Glaucoma Research Laboratory, Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA Shiley Eye Institute, Hamilton Glaucoma Center and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.

Abstract: Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.
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http://dx.doi.org/10.1097/APO.0000000000000438DOI Listing
September 2021

Rates of Circumpapillary Retinal Nerve Fiber Layer Thinning and Capillary Density Loss in Glaucomatous Eyes with Disc Hemorrhage.

Am J Ophthalmol 2021 Sep 26. Epub 2021 Sep 26.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, CA, United States. Electronic address:

Purpose: To investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in primary open angle glaucoma (POAG) with or without history of disc hemorrhage (DH).

Design: Observational cohort METHODS: In this longitudinal study, 34 eyes with DH and 134 eyes without DH that had at least 1.5 years of follow-up and three OCT and OCTA follow-up scans were enrolled. A linear mixed-effect model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes.

Results: Rates of whole image capillary density (wiCD) loss were faster in the DH group compared to non-DH group (mean difference (95% CI): -0.32 (-0.59,-0.04) %/year, P=0.027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P<0.05). There was no statistically significant difference in the global rate of cpRNFL thinning between the two groups (P=0.679). The mean rate of cpRNFL thinning was faster in the DH group compared to the non-DH group only in the inferotemporal sector (mean difference (95% CI): -1.01 (-1.62,-0.40) μm/year; P=0.001).

Conclusions: Mean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the two groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and POAG patients.
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http://dx.doi.org/10.1016/j.ajo.2021.09.013DOI Listing
September 2021

Central macular OCTA parameters in glaucoma.

Br J Ophthalmol 2021 Aug 23. Epub 2021 Aug 23.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA

Background/aims: To investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects.

Methods: One hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model.

Results: Axial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm, glaucoma suspect 0.29 (0.26 to 0.31) mm and POAG eyes 0.28 (0.27 to 0.30) mm (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p<0.05). In addition, a smaller FAZ area was associated with lower intraocular pressure (IOP) (p=0.026).

Conclusions: The FD300, but not the FAZ area was correlated with 10° central visual field mean deviation and foveal threshold in healthy, glaucoma suspect and POAG eyes. In contrast, a smaller FAZ area was associated with lower IOP.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319574DOI Listing
August 2021

Association of serum retinol concentration with normal-tension glaucoma.

Eye (Lond) 2021 Aug 12. Epub 2021 Aug 12.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Objectives: To evaluate the association between serum retinol concentration and normal-tension glaucoma (NTG).

Methods: A total of 345 study subjects were recruited in a prospective cross-sectional study: 101 patients with NTG, 106 patients with high-pressure primary open-angle glaucoma (POAG) and 138 healthy control subjects. Serum retinol concentration in fasting blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All study subjects were given complete ophthalmic examinations and diagnosed by two glaucoma sub-specialists.

Results: Serum retinol concentrations in NTG, POAG, and controls were 338.90 ± 103.23 ng/mL, 405.22 ± 114.12 ng/mL, and 408.84 ± 122.36 ng/mL respectively. NTG patients had lower serum retinol concentrations than POAG (p < 0.001) or healthy controls (p < 0.001). There was no statistical difference between the POAG and healthy controls (p = 0.780). Higher proportion of NTG patients (37.6%) than POAG (17.9%) or controls (21.7%) had serum retinol concentrations lower than 300 ng/mL. Serum retinol was positively correlated with optic nerve sheath diameter (ONSD) (r = 0.349, p = 0.001) in glaucoma patients and not associated with any other demographic features or ophthalmic biometric parameters in the NTG patients. Multivariate logistic regression showed that serum retinol (OR = 0.898, 95CI%: 0.851-0.947) was associated with incident NTG.

Conclusions: NTG patients had lower serum retinol concentrations. Serum retinol uniquely associated with NTG makes it a new potential option for the diagnosis and treatment of the disease.
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http://dx.doi.org/10.1038/s41433-021-01740-6DOI Listing
August 2021

Macular Thickness and Microvasculature Loss in Glaucoma Suspect Eyes.

Ophthalmol Glaucoma 2021 Jul 30. Epub 2021 Jul 30.

Hamilton Glaucoma Center and Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, California. Electronic address:

Purpose: To characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON).

Design: Prospective, longitudinal study.

Participants: Eight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years.

Methods: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model.

Main Outcome Measures: Change rates of macula GCC thickness and superficial vessel density.

Results: Significant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 μm/year; P = 0.025) and GON group (-0.79 μm/year; P = 0.058) were faster than those of the healthy group (-0.11 μm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease.

Conclusions: Whereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.
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http://dx.doi.org/10.1016/j.ogla.2021.07.009DOI Listing
July 2021

Optical microangiography and progressive retinal nerve fiber layer loss in primary open angle glaucoma.

Am J Ophthalmol 2021 Jul 25. Epub 2021 Jul 25.

Hamilton Glaucoma Center, Shiley Eye Institute, and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA, United States.

Purpose: To evaluate the association between optical microangiography (OMAG) measurements and progressive retinal nerve fiber layer (RNFL) loss in primary open angle glaucoma (POAG).

Design: Prospective case series METHODS: : Sixty-four eyes of 40 POAG patients (108 quadrants) with mild to moderate functional damage were longitudinally studied for at least 2 years and with a minimum of 3 optical coherence tomography (OCT) examinations. OMAG imaging was performed at the baseline visit. Effect of clinical parameters (age, gender, presence of systemic diseases, central corneal thickness, presence of disc hemorrhage, mean and fluctuation of intraocular pressure during follow-up), baseline hemifield mean deviation (MD), baseline quadrant OCT (retinal nerve fiber layer [RNFL] and ganglion cell inner plexiform layer [GCIPL] thickness) and OMAG (peripapillary and macular perfusion density [PD] and vessel density [VD]) on the rate of RNFL change was evaluated using linear mixed models.

Results: Average (±SD) MD, RNFL and GCIPL thickness of the analyzed quadrants at baseline were -5.5±2.9 dB, 96.5±17.9 µm, and 73.8±8.6 µm, respectively. Peripapillary PD and VD in the quadrant were 44.6±5.9% and 17.5±2.2 mm/mm respectively. Rate of quadrant RNFL change was -1.8±0.6 µm/year. Multivariate mixed models showed that lower peripapillary PD (coefficient: 0.08, p=0.01) and lower VD (coefficient: 0.21, p=0.02) were significantly associated with faster rate of RNFL loss.

Conclusions: Lower baseline peripapillary PD and VD measured using OMAG were significantly associated with a faster rate of RNFL loss in POAG. OMAG imaging provides useful information about the risk of glaucoma progression and the rate of disease worsening.
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http://dx.doi.org/10.1016/j.ajo.2021.07.023DOI Listing
July 2021

Agreement between Compass Fundus Perimeter New Grid and 10-2 Testing Protocols for Detecting Central Visual Field Defects.

Ophthalmol Glaucoma 2021 Jul 20. Epub 2021 Jul 20.

Hamilton Glaucoma Center, Shiley Eye Institute, and the Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California. Electronic address:

Purpose: To evaluate the agreement between Compass New Grid (NG) and 10-2 test protocols for detecting early glaucomatous defects in the central 10 degrees of the visual field (CVFD).

Design: Cross-sectional study.

Participants: A total of 123 eyes of 14 healthy individuals, 17 glaucoma suspects, and 32 glaucoma patients were enrolled.

Methods: Subjects performed NG and 10-2 Compass automated perimetry testing within 1 week. For both test protocols, total deviation (TD) and pattern deviation (PD) plot CVFDs were defined by 3 contiguous points with probabilities of <5%, <2%, <2% or <5%, <1%, <1%. Cohen's Kappa statistic was used to assess agreement between NG and 10-2 for identifying CVFDs. The Spectralis GMPE Hood Glaucoma Report (investigational software version) macula deviation analysis obtained within 1 year was used for calculating sensitivities and specificities of test protocols.

Main Outcome Measures: Protocols' agreement, sensitivity, and specificity.

Results: Fair to moderate agreement was observed between NG and 10-2 protocols for detecting presence of superior CVFDs on TD (k = 0.57) and PD (k = 0.26) plots and for detecting inferior CVFDs on TD (0.49) and PD (0.27) plots. With the use of OCT macula deviation maps, specificity for detecting CVFD was consistently higher with NG than 10-2 tests for TD plots of the superior hemifield (0.82 and 0.65), inferior hemifield (0.92 and 0.84), and PD plots of the superior hemifield (0.81 and 0.36) and inferior hemifield (0.86 and 0.52). Sensitivity of NG was consistently lower than TD plots of the superior hemifield (0.48 and 0.72), inferior hemifield (0.28 and 0.46), and PD plots of the superior hemifield (0.48 and 0.78) and inferior hemifield (0.20 and 0.52). By using pattern standard deviation (PSD) criterion, the mean PSD values for 10-2 and NG VF tests were 1.61 (95% confidence interval [CI], 1.26-1.96) and 1.81 (95% CI, 1.45-2.17) (P < 0.001), respectively.

Conclusions: Although the Compass NG detected fewer CVFDs than the 10-2 test protocol, it did detect CVFDs that were not observed in the Compass 24-2 test in patients with early glaucoma. Therefore, NG may be particularly useful in clinical situations when higher specificity is desired or PSD criterion is used.
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http://dx.doi.org/10.1016/j.ogla.2021.07.006DOI Listing
July 2021

Individualized Glaucoma Change Detection Using Deep Learning Auto Encoder-Based Regions of Interest.

Transl Vis Sci Technol 2021 07;10(8):19

Hamilton Glaucoma Center, Shiley Eye Institute, The Viterbi Family Department of Ophthalmology, UC San Diego, La Jolla, CA, USA.

Purpose: To compare change over time in eye-specific optical coherence tomography (OCT) retinal nerve fiber layer (RNFL)-based region-of-interest (ROI) maps developed using unsupervised deep-learning auto-encoders (DL-AE) to circumpapillary RNFL (cpRNFL) thickness for the detection of glaucomatous progression.

Methods: Forty-four progressing glaucoma eyes (by stereophotograph assessment), 189 nonprogressing glaucoma eyes (by stereophotograph assessment), and 109 healthy eyes were followed for ≥3 years with ≥4 visits using OCT. The San Diego Automated Layer Segmentation Algorithm was used to automatically segment the RNFL layer from raw three-dimensional OCT images. For each longitudinal series, DL-AEs were used to generate individualized eye-based ROI maps by identifying RNFL regions of likely progression and no change. Sensitivities and specificities for detecting change over time and rates of change over time were compared for the DL-AE ROI and global cpRNFL thickness measurements derived from a 2.22-mm to 3.45-mm annulus centered on the optic disc.

Results: The sensitivity for detecting change in progressing eyes was greater for DL-AE ROIs than for global cpRNFL annulus thicknesses (0.90 and 0.63, respectively). The specificity for detecting not likely progression in nonprogressing eyes was similar (0.92 and 0.93, respectively). The mean rates of change in DL-AE ROI were significantly faster than for cpRNFL annulus thickness in progressing eyes (-1.28 µm/y vs. -0.83 µm/y) and nonprogressing eyes (-1.03 µm/y vs. -0.78 µm/y).

Conclusions: Eye-specific ROIs identified using DL-AE analysis of OCT images show promise for improving assessment of glaucomatous progression.

Translational Relevance: The detection and monitoring of structural glaucomatous progression can be improved by considering eye-specific regions of likely progression identified using deep learning.
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http://dx.doi.org/10.1167/tvst.10.8.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300051PMC
July 2021

Optic Nerve Engraftment of Neural Stem Cells.

Invest Ophthalmol Vis Sci 2021 07;62(9):30

Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, United States.

Purpose: To evaluate the integrative potential of neural stem cells (NSCs) with the visual system and characterize effects on the survival and axonal regeneration of axotomized retinal ganglion cells (RGCs).

Methods: For in vitro studies, primary, postnatal rat RGCs were directly cocultured with human NSCs or cultured in NSC-conditioned media before their survival and neurite outgrowth were assessed. For in vivo studies, human NSCs were transplanted into the transected rat optic nerve, and immunohistology of the retina and optic nerve was performed to evaluate RGC survival, RGC axon regeneration, and NSC integration with the injured visual system.

Results: Increased neurite outgrowth was observed in RGCs directly cocultured with NSCs. NSC-conditioned media demonstrated a dose-dependent effect on RGC survival and neurite outgrowth in culture. NSCs grafted into the lesioned optic nerve modestly improved RGC survival following an optic nerve transection (593 ± 164 RGCs/mm2 vs. 199 ± 58 RGCs/mm2; P < 0.01). Additionally, RGC axonal regeneration following an optic nerve transection was modestly enhanced by NSCs transplanted at the lesion site (61.6 ± 8.5 axons vs. 40.3 ± 9.1 axons, P < 0.05). Transplanted NSCs also differentiated into neurons, received synaptic inputs from regenerating RGC axons, and extended axons along the transected optic nerve to incorporate with the visual system.

Conclusions: Human NSCs promote the modest survival and axonal regeneration of axotomized RGCs that is partially mediated by diffusible NSC-derived factors. Additionally, NSCs integrate with the injured optic nerve and have the potential to form neuronal relays to restore retinofugal connections.
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http://dx.doi.org/10.1167/iovs.62.9.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300061PMC
July 2021

Standard reliability and gaze tracking metrics in glaucoma and glaucoma suspects.

Am J Ophthalmol 2021 Jul 16. Epub 2021 Jul 16.

Hamilton Glaucoma Center, Shiley Eye Institute, and Viterbi Family Department of Ophthalmology, University of California San Diego.

Purpose: To compare standard reliability metrics and gaze tracking (GT) metrics on the Humphrey Field Analyzer (HFA).

Design: Retrospective cross-sectional study.

Methods: SETTING: VA Medical Center, San Diego.

Patient Population: 494 glaucoma and glaucoma suspect patients that had an HFA 24-2 SITA Fast visual field (VF) performed in both eyes.

Observation: Standard reliability metrics (fixation loss [FL], false positive [FP], and false negative [FN]) were compared to GT metrics (deviations 1-2 degrees [M1], deviations 3-5 degrees [M3], deviations >6 degrees [M6], and tracking failure frequency [TFF]).

Main Outcome Measures: Spearman's rank-based correlation coefficient and area under the receiver operating characteristic (AUROC) curves between standard and GT reliability metrics.

Results: The 95 percentile limits for GT metrics were 66.7% for M1, 67.5% for M3, 49.5% for M6, and 79.8% for TFF. There were statistically significant correlations between standard and GT reliability metrics using the 95 percentile as a binary cutoff for GT metrics. However, low Spearman correlation values and AUROC calculations suggest little clinical significance of the associations. FN increased as VF severity worsened (p<0.001). M6 was lower in eyes with mild compared to moderate and advanced VF loss (p=0.012).

Conclusions: GT metrics do not have a clinically significant association with standard reliability metrics. Both FN and M6 are influenced by VF severity. Aggregate GT metrics do not aid in reliability assessment. These findings suggest that GT metrics may provide an alternative or complementary measure of VF reliability.
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http://dx.doi.org/10.1016/j.ajo.2021.06.038DOI Listing
July 2021

Reversal of a glaucomatous optic disc pit.

Am J Ophthalmol Case Rep 2021 Sep 16;23:101143. Epub 2021 Jun 16.

Department of Ophthalmology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.

Purpose: To report a patient in whom a glaucomatous optic disc pit (ODP) disappeared spontaneously.

Observations: A 59-year-old Korean woman presented with primary open-angle glaucoma, an ODP, and deep superior cecocentral scotomas. She was treated with topical ocular hypotensive medications and followed. Twenty-eight months later, the superior cecocentral scotomas were not detectable with repeated visual field testing. With repeated optical coherence tomography (OCT), the ODP was narrower and shallower; partially filled with prelaminar tissue, there was an increase in the minimal rim width. At the final examination, the cecocentral scotomas reappeared, although prelaminar tissue continued to fill the ODP.

Conclusions And Importance: ODP can disappear spontaneously in glaucomatous eyes under ocular hypotensive treatment. However, this is not always associated with sustained visual field improvement.
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http://dx.doi.org/10.1016/j.ajoc.2021.101143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233205PMC
September 2021

Diurnal Variation of Retinal Vessel Density in Healthy Human Eyes.

J Glaucoma 2021 09;30(9):820-826

Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, CA.

Precis: A small increase in optic nerve head vessel density (VD), but not macular VD, in the evening compared with the morning is observed in healthy subjects.

Purpose: To evaluate the diurnal variation of the macular and optic nerve head (ONH) VD in healthy eyes as measured with optical coherence tomography angiography (OCT-A).

Methods: In this prospective study of healthy individuals older than 18 years old, VD parameters, including macular whole image vessel density, parafoveal vessel density, ONH whole image vessel density, ONH whole image capillary density, circumpapillary vessel density (cpVD), and circumpapillary capillary density, were measured with OCT-A at 4 time points throughout the day (8 am, 12 pm, 4 pm, and 8 pm).

Results: Twenty-nine healthy eyes were included from 15 subjects (mean age: 30.9 y). After adjustment for age and mean ocular perfusion pressure, a significant positive rate of change was found for cpVD (0.05%/h; P=0.027). In contrast, macular VD changes were not significantly different. When comparing morning (8 am and 12 pm) and evening (4 pm and 8 pm) measurements, there were small, but statistically significant, increases for all ONH measurements. The greatest increase was found for cpVD (0.58%; P=0.022). Significant but small increases in mean arterial pressure and mean ocular perfusion pressure were also observed.

Conclusions: There was a small increase in ONH VD, but not macular VD, in the evening compared with the morning in healthy human eyes. As the observed difference was within the measurement variability, our results suggest the timing of OCT-A examination does not affect retinal VD measurements.
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http://dx.doi.org/10.1097/IJG.0000000000001903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405550PMC
September 2021

Characteristics of Central Visual Field Progression in Eyes with Optic Disc Hemorrhage.

Am J Ophthalmol 2021 Jun 6;231:109-119. Epub 2021 Jun 6.

From the Hamilton Glaucoma Center (R.C.C.D., S.M., J.L.D., H.H., J.P., L.M.Z., A.K., T.N., R.N.W.), Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, California. Electronic address:

Purpose: To investigate the characteristics and rate of central visual field loss after optic disc hemorrhage (DH).

Design: Prospective cohort study.

Methods: Three hundred forty-three eyes of 220 subjects who had ≥3 years of follow-up with a minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and predefined zones were compared using linear mixed-effects models in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared with 24-2 VF loss using guided progression analysis.

Results: Thirty-nine eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 MD loss that were 3 times faster than non-DH eyes (mean difference -0.36 dB/year [95% confidence interval 0.54-0.18]; P < .001) and were 3.7 times more likely to progress (P = .002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in the DH group (30.8% vs. 20.5%) compared with the non-DH group (10.9% vs. 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes (P < .001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes.

Conclusion: Central VF loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In patients with glaucoma with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.
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http://dx.doi.org/10.1016/j.ajo.2021.05.026DOI Listing
June 2021

A Bibliometric and Mapping Analysis of Glaucoma Research between 1900 and 2019.

Ophthalmol Glaucoma 2021 May 31. Epub 2021 May 31.

Faculty of Optics and Optometry, Complutense University of Madrid, Madrid, Spain.

Purpose: To explore the relevance of scientific production on glaucoma using bibliometric tools.

Design: Bibliographic study.

Participants: Original articles published from 1900 through 2019.

Methods: We performed a search in Web of Science for documents published between 1900 and 2019. We used bibliometric indicators to explore documents production, dispersion, distribution, time of duplication, and annual growth, as characterized by Price's law of scientific literature growth, Lotka's law, the transient index, and the Bradford model. We also calculated the participation index of different countries and institutions. Finally, we explored with bibliometric mapping the co-occurrence networks for the most frequently used terms in glaucoma research.

Main Outcome Measures: Bibliometric indicators for individuals, institutions, and countries.

Results: A total of 33 631 original articles were collected from the timeframe 1900 through 2019. Price's law showed an exponential growth. Scientific production was adjusted better to exponential growth (r = 0.967) than linear growth (r = 0.755). Literature on glaucoma research increased its growth in the last 30 years at a rate of 5.1% per year with a production that doubled its size every 13.9 years. The transience index was 60.08%; this indicates that most of the scientific production is the output of very few authors. Bradford's law showed a high concentration of articles published in a small core of specialized journals. Lotka's law indicated that the distribution of authors is concentrated heavily in small producers. The United States and University of London demonstrated the highest production of original articles. Map network visualization showed the generated term map detailing clusters of closely related terms.

Conclusions: Glaucoma literature has grown exponentially. A very high rate of transience was found that indicates the presence of numerous authors who sporadically publish on this topic. No evidence of a saturation point in the glaucoma literature was observed.
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http://dx.doi.org/10.1016/j.ogla.2021.05.008DOI Listing
May 2021

Implanted Microsensor Continuous IOP Telemetry Suggests Gaze and Eyelid Closure Effects on IOP-A Preliminary Study.

Invest Ophthalmol Vis Sci 2021 05;62(6)

Department of Ophthalmology, University Hospital Magdeburg, Germany.

Purpose: To explore the effect of gaze direction and eyelid closure on intraocular pressure (IOP).

Methods: Eleven patients with primary open-angle glaucoma previously implanted with a telemetric IOP sensor were instructed to view eight equally-spaced fixation targets each at three eccentricities (10°, 20°, and 25°). Nine patients also performed eyelid closure. IOP was recorded via an external antenna placed around the study eye. Differences of mean IOP between consecutive gaze positions were calculated. Furthermore, the effect of eyelid closure on gaze-dependent IOP was assessed.

Results: The maximum IOP increase was observed at 25° superior gaze (mean ± SD: 4.4 ± 4.9 mm Hg) and maximum decrease at 25° inferonasal gaze (-1.6 ± 0.8 mm Hg). There was a significant interaction between gaze direction and eccentricity (P = 0.003). Post-hoc tests confirmed significant decreases inferonasally for all eccentricities (mean ± SEM: 10°: -0.7 ± 0.2, P = 0.007; 20°: -1.1 ± 0.2, P = 0.006; and 25°: -1.6 ± 0.2, P = 0.006). Eight of 11 eyes showed significant IOP differences between superior and inferonasal gaze at 25°. IOP decreased during eyelid closure, which was significantly lower than downgaze at 25° (mean ± SEM: -2.1 ± 0.3 mm Hg vs. -0.7 ± 0.2 mm Hg, P = 0.014).

Conclusions: Our data suggest that IOP varies reproducibly with gaze direction, albeit with patient variability. IOP generally increased in upgaze but decreased in inferonasal gaze and on eyelid closure. Future studies should investigate the patient variability and IOP dynamics.
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http://dx.doi.org/10.1167/iovs.62.6.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107486PMC
May 2021

Rates of Retinal Nerve Fiber Layer Thinning in Distinct Glaucomatous Optic Disc Phenotypes in Early Glaucoma.

Am J Ophthalmol 2021 Apr 25;229:8-17. Epub 2021 Apr 25.

From the Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California (R.C.C.D., S.M., E.E., J.L.D., H.H., J.A.P., A.K., T.N., R.N.W.), San Diego, La Jolla, California. Electronic address:

Purpose: To compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among 4 glaucomatous optic disc phenotypes in early glaucoma.

Design: Clinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into 4 types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed effects model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes.

Results: After adjusting for confounders, the SS group (mean [95% CI]: -1.01 [-1.30, -0.73] µm/y) had the fastest mean rate of global cpRNFL thinning followed by FI (-0.77 [-0.97, -0.57] µm/y), MY (0.59 [-0.81, -0.36] µm/y), and GE (-0.58 [-0.75, -0.40] µm/y) at P < .001. The inferior temporal sector had the fastest rate of cpRNFL thinning among the regional measurements except for the MY group (-0.68 [-1.10, -0.26] µm/y, P = .002). In the multivariable analysis, GE (P = .002) and MY (P = .010) phenotypes were associated with significantly slower global rates of cpRNFL thinning compared with the SS phenotype.

Conclusions: Rates of cpRNFL thinning were different among the 4 glaucomatous optic disc phenotypes. Those patients with early glaucoma with SS phenotype have the fastest cpRNFL thinning. These patients may benefit from more frequent monitoring and the need to advance therapy if cpRNFL thinning is detected.
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http://dx.doi.org/10.1016/j.ajo.2021.04.010DOI Listing
April 2021

Deep Learning Estimation of 10-2 and 24-2 Visual Field Metrics Based on Thickness Maps from Macula OCT.

Ophthalmology 2021 Nov 23;128(11):1534-1548. Epub 2021 Apr 23.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla, California. Electronic address:

Purpose: To develop deep learning (DL) systems estimating visual function from macula-centered spectral-domain (SD) OCT images.

Design: Evaluation of a diagnostic technology.

Participants: A total of 2408 10-2 visual field (VF) SD OCT pairs and 2999 24-2 VF SD OCT pairs collected from 645 healthy and glaucoma subjects (1222 eyes).

Methods: Deep learning models were trained on thickness maps from Spectralis macula SD OCT to estimate 10-2 and 24-2 VF mean deviation (MD) and pattern standard deviation (PSD). Individual and combined DL models were trained using thickness data from 6 layers (retinal nerve fiber layer [RNFL], ganglion cell layer [GCL], inner plexiform layer [IPL], ganglion cell-IPL [GCIPL], ganglion cell complex [GCC] and retina). Linear regression of mean layer thicknesses were used for comparison.

Main Outcome Measures: Deep learning models were evaluated using R and mean absolute error (MAE) compared with 10-2 and 24-2 VF measurements.

Results: Combined DL models estimating 10-2 achieved R of 0.82 (95% confidence interval [CI], 0.68-0.89) for MD and 0.69 (95% CI, 0.55-0.81) for PSD and MAEs of 1.9 dB (95% CI, 1.6-2.4 dB) for MD and 1.5 dB (95% CI, 1.2-1.9 dB) for PSD. This was significantly better than mean thickness estimates for 10-2 MD (0.61 [95% CI, 0.47-0.71] and 3.0 dB [95% CI, 2.5-3.5 dB]) and 10-2 PSD (0.46 [95% CI, 0.31-0.60] and 2.3 dB [95% CI, 1.8-2.7 dB]). Combined DL models estimating 24-2 achieved R of 0.79 (95% CI, 0.72-0.84) for MD and 0.68 (95% CI, 0.53-0.79) for PSD and MAEs of 2.1 dB (95% CI, 1.8-2.5 dB) for MD and 1.5 dB (95% CI, 1.3-1.9 dB) for PSD. This was significantly better than mean thickness estimates for 24-2 MD (0.41 [95% CI, 0.26-0.57] and 3.4 dB [95% CI, 2.7-4.5 dB]) and 24-2 PSD (0.38 [95% CI, 0.20-0.57] and 2.4 dB [95% CI, 2.0-2.8 dB]). The GCIPL (R = 0.79) and GCC (R = 0.75) had the highest performance estimating 10-2 and 24-2 MD, respectively.

Conclusions: Deep learning models improved estimates of functional loss from SD OCT imaging. Accurate estimates can help clinicians to individualize VF testing to patients.
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http://dx.doi.org/10.1016/j.ophtha.2021.04.022DOI Listing
November 2021

Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

J Glaucoma 2021 06;30(6):e276-e284

Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California San Diego, San Diego, CA.

Precis: Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma.

Purpose: The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes.

Materials And Methods: Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups.

Results: Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001).

Conclusions: SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.
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http://dx.doi.org/10.1097/IJG.0000000000001860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169636PMC
June 2021

The influence of axial myopia on optic disc characteristics of glaucoma eyes.

Sci Rep 2021 04 23;11(1):8854. Epub 2021 Apr 23.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0946, USA.

This study characterizes differences in glaucomatous eyes with and without high axial myopia using custom automated analysis of OCT images. 452 eyes of 277 glaucoma patients were stratified into non (n = 145 eyes), mild (n = 214 eyes), and high axial myopia (axial length (AL) > 26 mm, n = 93 eyes). Optic disc ovality index, tilt and rotation angle of Bruch´s membrane opening (BMO) and peripapillary choroidal thickness (PCT) were calculated using automated and deep learning strategies. High myopic optic discs were more oval and had larger BMO tilt than mild and non-myopic discs (both p < 0.001). Mean PCT was thinnest in high myopic eyes followed by mild and non-myopic eyes (p < 0.001). BMO rotation angle, global retinal nerve fiber layer (RNFL) thickness and BMO-minimum rim width (MRW) were similar among groups. Temporal RNFL was thicker and supranasal BMO-MRW was thinner in high myopic eyes. BMO tilt and PCT showed moderate and temporal RNFL and nasal BMO-MRW showed weak but significant associations with AL in multivariable analyses (all p < 0.05). Large BMO tilt angle and thin PCT are characteristics of highly myopic discs and were not associated with severity of glaucoma. Caution should be exercised when using sectoral BMO-MRW and RNFL thickness for glaucoma management decisions in myopic eyes.
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http://dx.doi.org/10.1038/s41598-021-88406-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065167PMC
April 2021

Review of glaucoma medication adherence monitoring in the digital health era.

Br J Ophthalmol 2021 Apr 15. Epub 2021 Apr 15.

Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, USA

Current glaucoma treatments aim to lower intraocular pressure, often with topical ocular hypotensive medications. Unfortunately, the effectiveness of these medications depends on sustained patient adherence to regimens which may involve instilling multiple medications several times daily. Patient adherence to glaucoma medications is often low. Recent innovations in digital sensor technologies have been leveraged to confirm eyedrop medication usage in real-time and relay this information back to providers. Some sensors have also been designed to deliver medication reminders and notifications as well as assist with correct eyedrop administration technique. Here, we review recent innovations targeted at improving glaucoma medication adherence and discuss their limitations.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517037PMC
April 2021

Racial Differences in the Rate of Change in Anterior Lamina Cribrosa Surface Depth in the African Descent and Glaucoma Evaluation Study.

Invest Ophthalmol Vis Sci 2021 04;62(4):12

Department of Ophthalmology and Visual Science, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.

Purpose: The purpose of this study was to determine if the rate of change in the depth of the surface of the lamina cribrosa due to glaucomatous remodeling differs between glaucoma patients of African descent (AD) and European descent (ED).

Methods: There were 1122 images taken longitudinally over an average of 3 years (range = 0.9-4.1 years) from 122 patients with glaucoma followed in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Intervention and Glaucoma Study (DIGS) were automatically segmented to compute anterior lamina cribrosa surface depth (ALCSD). The rate of ALCSD change was compared across racial groups after adjusting for baseline characteristics known to be associated with ALCSD or disease progression (visual field, ALCSD, corneal thickness, optic disk size, and age).

Results: After adjusting for all other covariates, the ED group had significantly greater ALCSD posterior migration (deepening) than the AD group (difference = 2.57 µm/year, P = 0.035). There was a wider range of ALCSD change in the ED compared with the AD group, and more individuals had greater magnitude of both deepening and shallowing. No other covariates measured at baseline had independent effects on the longitudinal changes in ALCSD (baseline visual field severity, baseline ALCSD, corneal thickness, Bruch's membrane opening [BMO] area, or age).

Conclusions: Glaucomatous remodeling of the lamina cribrosa differs between AD and ED patients with glaucoma. Unlike the cross-sectional associations seen with aging, in which a deeper ALCSD was seen with age in the ED group, glaucomatous remodeling in this longitudinal study resulted in more posterior migration of ALCSD in ED compared to AD patients.
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http://dx.doi.org/10.1167/iovs.62.4.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039570PMC
April 2021

OCT Angiography Artifacts in Glaucoma.

Ophthalmology 2021 Oct 2;128(10):1426-1437. Epub 2021 Apr 2.

Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California. Electronic address:

Purpose: To determine the prevalence of different types of artifacts seen in OCT angiography (OCTA) images of healthy and glaucoma eyes and evaluate the characteristics associated with poor-quality images.

Design: Retrospective study.

Participants: A total of 649 eyes of 368 healthy, glaucoma suspect, and glaucoma patients.

Methods: Angiovue (Optovue Inc) high-density (HD) and non-HD optic nerve head and macula OCTA images of participants were evaluated by 4 expert reviewers for the presence of different artifacts, including eye movement, defocus, shadow, decentration, segmentation error, blink, and Z offset in the superficial vascular layer. Each OCTA scan was designated to have good or poor quality based on the presence of artifacts. The association of demographic and ocular characteristics with the likelihood of obtaining poor-quality OCTA images was evaluated.

Main Outcome Measures: The prevalence of OCTA artifacts and the factors associated with increased likelihood of capturing poor-quality OCTA images.

Results: A total of 5263 OCTA images were evaluated. Overall, 33.9% of the OCTA images had poor quality. The majority of images with acceptable quality scores (QS ≥ 4) had no artifacts (76.6%). Other images had 1 (13.6%) or 2 or more artifacts (9.8%). Older age (P < 0.001), male gender (P = 0.045), worse visual field mean deviation (P < 0.001), absence of eye tracking (P < 0.001), and macular scan area (P < 0.001) were associated with a higher likelihood of obtaining poor-quality images. In images with acceptable QS, the commercially available quality measures including QS and signal strength index had the area under the receiver operating characteristic curves of 0.65 (95% confidence interval [CI], 0.62-0.69) and 0.70 (95% CI, 0.68-0.73) to detect good-quality images, respectively.

Conclusions: OCTA artifacts associated with poor-quality images are frequent, and their prevalence is affected by ocular and patient characteristics. One should not rely solely on the quantitative assessments that are provided automatically by OCTA instruments. A systematic scan review should be conducted to ensure appropriate interpretation of OCTA images. Given the high prevalence of poor-quality OCTA images, the images should be reacquired whenever an apparent and correctable artifact is present on a captured image.
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http://dx.doi.org/10.1016/j.ophtha.2021.03.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463411PMC
October 2021

Agreement Between 10-2 and 24-2C Visual Field Test Protocols for Detecting Glaucomatous Central Visual Field Defects.

J Glaucoma 2021 06;30(6):e285-e291

The Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, University of California, San Diego, La Jolla, CA.

Precis: Moderate to substantial agreement between 10-2 and 24-2C perimetry for detecting central field defects suggests that adding central test points to the 24-2 protocol may improve efficiency of visual field (VF) testing for glaucoma management.

Purpose: The purpose of this study was to assess agreement between Humphrey Visual Field Analyzer 10-2 and 24-2C test protocols for detecting glaucomatous defects in the central 10 degrees of the visual field (CVFDs).

Materials And Methods: VFs from 165 eyes of 18 healthy individuals, 12 glaucoma suspects and 62 glaucoma patients who completed 10-2 and 24-2C VF testing protocols within 6 months were included. CVFDs on 10-2 and 24-2C (within the central 22 points) test grids required a cluster of 3 contiguous points with P<5%, 5%, and 1% or <5%, 2%, and 2% within a hemifield on the total deviation (TD) or pattern deviation (PD) plot. Cohen kappa (k) was used to assess agreement between 10-2 and 24-2C test grids in identifying CVFDs. Specificity of each testing strategy was assessed in VFs from healthy eyes.

Results: CVFDs in suspect and glaucoma eyes were combined and reported as localized to superior, inferior or both hemifields based on TD and PD plots for 10-2 and 24-2C test grids. Moderate to substantial agreement was observed between 10-2 and 24-2C grids for detecting any CVFD from PD (k=0.551) and TD (k=0.651) plots. Specificity was high in healthy eyes ranging from 0.94 to 1.0 for both test protocols.

Conclusion: Substantial agreement for identifying CVFDs using the 24-2C and 10-2 protocols suggests that combining tests by adding central test points to the 24-2 test grid may supplant the need for 2 perimetry regimens for detecting central and peripheral glaucomatous VF damage.
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http://dx.doi.org/10.1097/IJG.0000000000001844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169576PMC
June 2021

The effect of daily life activities on intraocular pressure related variations in open-angle glaucoma.

Sci Rep 2021 03 23;11(1):6598. Epub 2021 Mar 23.

Glaucoma Research Center, Montchoisi Clinic, Swiss Visio, Lausanne, Switzerland.

The recent advent of continuous intraocular pressure (IOP) telemetry has led to an increased awareness of the importance of IOP fluctuations, and theories have emerged that IOP variations could play as much a role in glaucoma progression as the mean level of IOP. The aim of the present study was to evaluate the direct effect of common daily activities on IOP-related profiles. Primary open-angle glaucoma and glaucoma suspect patients were prospectively enrolled from specialist clinics at the University of California San Diego (UCSD), USA. Patients were fitted with a SENSIMED Triggerfish (TF) contact lens sensor (CLS) and were instructed to return to their usual daily activities for 24 h. They were asked to record each specific activity or event in a diary. The protocol was repeated twice. The following events were recorded: "walking/cycling", "resistance training", "yoga/meditation", and "emotional stress". CLS measurements recorded 60-to-30 min prior to each event were used as a baseline reference, and all IOP-related fluctuations for 120 min after the start of each event were reported in relation to this reference. Forty relevant events from 22 CLS recordings in 14 patients were retrieved from the diaries. Walking/cycling (n = 10) caused a small but statistically significant elevation of the IOP-related profile during the activity (p = 0.018). Resistance training (n = 11) caused a persistent elevation of the IOP-related profile from the onset of the activity (p = 0.005) through 120 min after the activity was stopped (p = 0.007). Yoga/meditation (n = 4) caused a sustained drop in the IOP-related profiles through to 120 min, although this was not statistically significant (p > 0.380). Emotional stress (n = 13) was associated with a gradual elevation of the IOP-related profile from the start of the stressful stimulus. Both early and late variations were statistically significant (p = 0.038 and p = 0.021, respectively). The present study suggests that emotional stress and resistance training may be associated with persistent IOP-related profile elevation.
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http://dx.doi.org/10.1038/s41598-021-85980-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988182PMC
March 2021
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