Publications by authors named "Brian J Song"

30 Publications

  • Page 1 of 1

Intrasession repeatability and intersession reproducibility of peripapillary OCTA vessel parameters in non-glaucomatous and glaucomatous eyes.

Br J Ophthalmol 2020 Sep 11. Epub 2020 Sep 11.

Ophthalmology, University of Southern California Keck School of Medicine, Los Angeles, California, USA

Objective: To compare intrasession repeatability versus intersession reproducibility of the peripapillary vessel parameters using optical microangiography-based optical coherence tomography angiography (OCTA) in non-glaucomatous and glaucomatous eyes.

Methods: In an observational, longitudinal study, peripapillary OCTA scans were collected to evaluate intrasession repeatability and intersession reproducibility using within-eye coefficient of variation (CV) and intraclass correlation coefficient (ICC). Images were quantified using a custom research-oriented quantification software calculating vessel area density (VAD) and flux and a commercially developed, clinic-oriented quantification software (Cirrus 11.0, Carl Zeiss Meditec) calculating perfusion density (PD) and flux index (FI). Effect of signal strength on the reliability of OCTA parameters was also evaluated.

Results: Among 120 non-glaucomatous eyes, intrasession CV were 4.2% for VAD, 5.3% for flux, 1.5% for PD and 2.0% for FI. The intersession CV were 6.5% for VAD, 8.0% for flux, 2.0% for PD and 3.2% for FI. The intrasession ICC ranged from 0.928 to 0.945, and intersession ICC ranged from 0.811 to 0.866. From 118 glaucomatous eyes, intrasession CV was 9.0% for VAD, 10.3% for flux, 1.7% for PD and 2.3% for FI. The intersession CV was 12.1% for VAD, 14.2% for flux, 2.3% for PD and 3.5% for FI. The intrasession ICC ranged from 0.904 to 0.972, and intersession ICC ranged from 0.855 to 0.955. Signal strength was significantly positively associated with OCTA vessel parameters (p<0.0001) for both groups.

Conclusion: Peripapillary OCTA vessel parameters had greater intrasession repeatability compared to intersession reproducibility in both non-glaucomatous and glaucomatous eyes. The built-in commercially developed quantification software demonstrated greater agreement than the custom research-oriented quantification software.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317181DOI Listing
September 2020

Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma.

J Glaucoma 2019 05;28(5):473-480

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School.

PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma.

Purpose: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma.

Patients And Methods: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted.

Results: In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14).

Conclusions: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.
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http://dx.doi.org/10.1097/IJG.0000000000001225DOI Listing
May 2019

A Practical Approach to Retinal Dystrophies.

Adv Exp Med Biol 2018;1085:245-259

Jonas Children's Vision Care, Bernard & Shirlee Brown Glaucoma Laboratory, Columbia Stem Cell Initiative-Departments of Ophthalmology, Biomedical Engineering, Pathology & Cell Biology, Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Genomic approaches to developing new diagnostic and therapeutic strategies in retinal dystrophies are among the most advanced applications of genetics (Tsang SH, Gouras P (1996) Molecular physiology and pathology of the retina. In: Duane TD, Tasman W, Jaeger AE (eds) Duane's clinical opthalmology. Lippincott-Raven, Philadelphia). The notion that "nothing can be done" for patients with retinal dystrophies is no longer true. Electrophysiological testing and autofluorescence imaging help to diagnose and predict the patient's course of disease. Better phenotyping can contribute to better-directed, cost-efficient genotyping. Combining fundoscopy, autofluorescent imaging, and electrophysiological testing is essential in approaching patients with retinal dystrophies. Emerging are new gene-based treatments for these devastating conditions.
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http://dx.doi.org/10.1007/978-3-319-95046-4_51DOI Listing
July 2019

Diabetic Retinopathy Assessment Variability Among Eye Care Providers in an Urban Teleophthalmology Program.

Telemed J E Health 2019 04 24;25(4):301-308. Epub 2018 Jul 24.

4 Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston, Massachusetts.

Background: Teleophthalmology is an evidence-based method for diabetic eye screening. It is unclear whether the type of eye care provider performing teleophthalmology interpretation produces significant variability.

Introduction: We assessed grading variability between an optometrist, general ophthalmologist, and retinal specialist using images from an urban, diabetic retinopathy teleophthalmology program.

Methods: Three readers evaluated digital retinal images in 100 cases (178 eyes from 90 patients with type 2 diabetes). Fisher's exact test, percent agreement, and the observed proportion of positive (P) or negative agreement (P) were used to assess variability.

Results: Among cases deemed gradable by all three readers (n = 65), there was substantial agreement on absence of any retinopathy (88% ± 4.6%, P = 0.91-0.95), presence of moderate nonproliferative or worse retinopathy (87% ± 3.9%, P = 0.67-1.00), and presence of macular edema (99% ± 0.9%, P = 0.67-1.00). There was limited agreement regarding presence of referable nondiabetic eye pathology (61% ± 11%, P = 0.21-0.59) and early, nonroutine referral for a follow-up clinical eye exam (66% ± 8.1%, P = 0.19-0.54). Among all cases (n = 100), there was acceptable agreement regarding which had gradable images (77% ± 5.0%, P = 0.50-0.90).

Discussion: Inclusion of multiple types of eye care providers as teleophthalmology readers is unlikely to produce significant variability in the assessment of diabetic retinopathy among high-quality images. Greater variability was found regarding image gradability, nondiabetic eye pathology, and recommended clinical referral times.

Conclusions: Our results suggest that more extensive training and uniform referral standards are needed to improve consensus on image gradability, referable nondiabetic eye pathology, and recommended clinical referral times.
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http://dx.doi.org/10.1089/tmj.2018.0019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482899PMC
April 2019

Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle Glaucoma Have an Arterial Origin.

Am J Ophthalmol 2018 03 9;187:108-116. Epub 2018 Jan 9.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To analyze optic disc hemorrhages (DH) associated with primary open-angle glaucoma by quantifying their geometric profile and comparing their densitometry with hemorrhages from retinal vein occlusions (RVO) and retinal macroaneurysms (MA), which have venous and arterial sources of bleeding, respectively.

Design: Retrospective cross-sectional study.

Methods: Setting: Massachusetts Eye & Ear.

Population: Fundus images of DH (n = 40), MA (n = 14), and RVO (n = 25) were identified. Patient clinical backgrounds and demographics were obtained.

Main Outcome Measures: Grayscale pixel intensity units of hemorrhages and adjacent arteriole and venule over the same background tissue were measured. Densitometry differentials (arteriole or venule minus hemorrhage [ΔA and ΔV, respectively]) were calculated. The ratios of length (radial) to midpoint width for DH were calculated. Mean ΔA and ΔV between groups were compared with t tests. Multiple linear regression assessed the relation of retinal hemorrhage diagnosis to ΔA and ΔV and of DH shape to ΔA and ΔV.

Results: Mean (± standard deviation) ΔA and ΔV for DH (6.9 ± 7.1 and -4.7 ± 8.0 pixel intensity units, respectively) and MA (5.3 ± 5.9 and -6.0 ± 4.6, respectively) were comparable (P ≥ .43). Mean ΔA (14.6 ± 7.7) and ΔV (6.4 ± 6.3) for RVO were significantly higher compared to DH and MA (P < .0001) and remained significant in multivariable analyses. A unit increase in DH length-to-width ratio was associated with 1.2 (0.5) and 1.3 (0.5) pixel intensity unit (standard error) decrease in ΔA and ΔV, respectively (P ≤ .014).

Conclusions: DH have densitometry profiles comparable to MA and different from RVO, suggesting that DH in glaucoma have an arterial origin.
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http://dx.doi.org/10.1016/j.ajo.2017.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754625PMC
March 2018

A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation to Aid Glaucoma Diagnosis.

J Med Syst 2017 Dec 7;42(1):20. Epub 2017 Dec 7.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.

This paper proposes a novel Adaptive Region-based Edge Smoothing Model (ARESM) for automatic boundary detection of optic disc and cup to aid automatic glaucoma diagnosis. The novelty of our approach consists of two aspects: 1) automatic detection of initial optimum object boundary based on a Region Classification Model (RCM) in a pixel-level multidimensional feature space; 2) an Adaptive Edge Smoothing Update model (AESU) of contour points (e.g. misclassified or irregular points) based on iterative force field calculations with contours obtained from the RCM by minimising energy function (an approach that does not require predefined geometric templates to guide auto-segmentation). Such an approach provides robustness in capturing a range of variations and shapes. We have conducted a comprehensive comparison between our approach and the state-of-the-art existing deformable models and validated it with publicly available datasets. The experimental evaluation shows that the proposed approach significantly outperforms existing methods. The generality of the proposed approach will enable segmentation and detection of other object boundaries and provide added value in the field of medical image processing and analysis.
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http://dx.doi.org/10.1007/s10916-017-0859-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719827PMC
December 2017

The ISNT Rule: How Often Does It Apply to Disc Photographs and Retinal Nerve Fiber Layer Measurements in the Normal Population?

Am J Ophthalmol 2017 Dec 23;184:19-27. Epub 2017 Sep 23.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: To determine what percentage of normal eyes follow the ISNT rule, and whether ISNT rule variants may be more generalizable to the normal population.

Design: Cross-sectional study.

Methods: Setting: Institutional setting.

Study Population: Total of 110 normal subjects.

Observation Procedures: Neuroretinal rim assessments from disc photographs and retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography.

Main Outcome Measures: The percentages of subjects that obeyed the ISNT rule and its variants.

Results: The ISNT rule is only valid for 37.0% of disc photograph rim assessments and 43.8% of RNFL measurements. Deviation of the nasal sector from the expected ISNT pattern was a major cause for the ISNT rule not being obeyed for both rim and RNFL assessments. Specifically, 10.9% of subjects had wider nasal rims than the inferior rims, 29.4% had wider nasal rims than the superior rims, 14.7% had narrower nasal rims than the temporal rims, and 42.9% had thinner nasal RNFLs compared to the temporal quadrant. Exclusion of the nasal quadrant from the ISNT rule significantly increased the validity of ISNT variant rules, with 70.9% and 76.4% of disc photographs following the IST rule and the IS rule, respectively. Similarly, for RNFL thickness, 70.9% and 71.8% of patients followed the IST and IS rule, respectively.

Conclusions: The ISNT rule is only valid for about a third of disc photographs and less than half of RNFL measurements in normal patients. ISNT rule variants, such as the IST and IS rule, may be considered, as they are valid in more than 70% of patients.
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http://dx.doi.org/10.1016/j.ajo.2017.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705386PMC
December 2017

Presence and Risk Factors for Glaucoma in Patients with Diabetes.

Curr Diab Rep 2016 12;16(12):124

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA.

Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure-the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients.
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http://dx.doi.org/10.1007/s11892-016-0815-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310929PMC
December 2016

Acquired Corneal Neuropathy and Photoallodynia Associated With Malposition of an Ex-PRESS Shunt.

J Glaucoma 2017 Jan;26(1):e19-e21

*Warren Alpert Medical School of Brown University, Providence, RI †Department of Ophthalmology, New England Eye Center/Tufts Medical Center, Tufts University School of Medicine ‡Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.

Purpose: Corneal neuropathy is a recently described disease process that is not well understood and is likely underdiagnosed as a result. This is the first reported case of an acquired corneal neuropathy associated with malposition of an Ex-PRESS shunt.

Methods: A single case report.

Results: We report the case of a 50-year-old man with a history of multiple procedures for glaucoma who subsequently developed photoallodynia and corneal neuropathy in association with malposition of an Ex-PRESS shunt in the peripheral cornea. Laser confocal microscopy (HRT3/RCM) of the cornea showed the presence of neuromas, decreased nerve density, and a significant increase of dendritiform immune cells consistent with our diagnosis. Initial treatment with steroid pulse therapy did not result in decreased inflammation or symptomatic improvement leading to surgical explantation of the shunt. One month after surgery, there was noticeable improvement in the patient's pain and photoallodynia (approximately 40%) as well as the abnormalities seen on confocal microscopy.

Conclusions: We hypothesize that poor Ex-PRESS shunt positioning can act as a nidus for corneal inflammation, resulting in corneal neuropathy and lowering of the nociception threshold.
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http://dx.doi.org/10.1097/IJG.0000000000000502DOI Listing
January 2017

Trabeculectomy and Combined Phacoemulsification-Trabeculectomy: Outcomes and Risk Factors for Failure in Primary Angle Closure Glaucoma.

J Glaucoma 2016 09;25(9):763-9

*Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California in Los Angeles, Los Angeles, CA †Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA ‡Department of Medicine, Banner Good Samaritan Medical Center, Phoenix, AZ.

Purpose: To evaluate tonometric outcomes of patients with primary angle closure glaucoma (PACG) who have undergone trabeculectomy with mitomycin C (MMC) with and without concurrent phacoemulsification and to identify risk factors for postoperative failure.

Patients And Methods: Retrospective cohort study of 44 eyes of 33 phakic patients who underwent trabeculectomy with MMC with or without combined phacoemulsification for PACG. The primary endpoint was qualified tonometric success at 12 months according to predefined criteria. LogMAR visual acuity, number of glaucoma medications, and postoperative complications were also evaluated. Cox proportional hazard regression analysis was performed to identify potential risk factors for trabeculectomy failure.

Results: Mean intraocular pressure (IOP) decreased from 21.3±7.9 to 12.2±3.9 mm Hg at 12 months (P<0.001) in all patients. A significant reduction in mean number of glaucoma medications (P<0.001) was also seen. There was no change in logMAR visual acuity (P=0.39) after 12 months. There were no significant intergroup differences in mean IOP (P=0.42), number of glaucoma medications (P=0.85), or logMAR visual acuity (P=0.42) between the trabeculectomy versus combined surgery groups after 12 months. Increased age, greater baseline IOP, limbus-based conjunctival flaps, and MMC duration >1 minute were associated with decreased risk of surgical failure. Concurrent phacoemulsification at the time of trabeculectomy did not alter tonometric success or rate of complications.

Conclusions: In phakic patients with PACG, trabeculectomy with MMC significantly reduces IOP and number of glaucoma medications at 12 months without change in visual acuity. However, success rates are modest when based on more demanding tonometric criteria.
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http://dx.doi.org/10.1097/IJG.0000000000000493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001924PMC
September 2016

Regional Image Features Model for Automatic Classification between Normal and Glaucoma in Fundus and Scanning Laser Ophthalmoscopy (SLO) Images.

J Med Syst 2016 Jun 16;40(6):132. Epub 2016 Apr 16.

Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, Department of Ophthalmology, Boston, MA, USA.

Glaucoma is one of the leading causes of blindness worldwide. There is no cure for glaucoma but detection at its earliest stage and subsequent treatment can aid patients to prevent blindness. Currently, optic disc and retinal imaging facilitates glaucoma detection but this method requires manual post-imaging modifications that are time-consuming and subjective to image assessment by human observers. Therefore, it is necessary to automate this process. In this work, we have first proposed a novel computer aided approach for automatic glaucoma detection based on Regional Image Features Model (RIFM) which can automatically perform classification between normal and glaucoma images on the basis of regional information. Different from all the existing methods, our approach can extract both geometric (e.g. morphometric properties) and non-geometric based properties (e.g. pixel appearance/intensity values, texture) from images and significantly increase the classification performance. Our proposed approach consists of three new major contributions including automatic localisation of optic disc, automatic segmentation of disc, and classification between normal and glaucoma based on geometric and non-geometric properties of different regions of an image. We have compared our method with existing approaches and tested it on both fundus and Scanning laser ophthalmoscopy (SLO) images. The experimental results show that our proposed approach outperforms the state-of-the-art approaches using either geometric or non-geometric properties. The overall glaucoma classification accuracy for fundus images is 94.4% and accuracy of detection of suspicion of glaucoma in SLO images is 93.9 %.
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http://dx.doi.org/10.1007/s10916-016-0482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834108PMC
June 2016

Plasma bioavailability and regional brain distribution of polyphenols from apple/grape seed and bilberry extracts in a young swine model.

Mol Nutr Food Res 2015 Dec 28;59(12):2432-47. Epub 2015 Oct 28.

Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.

Scope: The pharmacokinetics, bioavailability, and regional brain distribution of polyphenols from apple-grape seed extract (AGSE) mixture and bilberry extract were studied after 3 weeks of dosing in weanling pigs.

Materials And Methods: Weanling piglets were treated for 3 weeks with extracts of (AGSE) or bilberry extracts, using a physiological (27.5 mg/kg) or supplement (82.5 mg/kg) dose. A 24-h pharmacokinetic study was conducted and brain tissue was harvested. Major flavan-3-ol and flavonol metabolites including catechin-O-β-glucuronide, epicatechin-O-β-glucuronide, 3'O-methyl-catechin-O-β-glucuronide, 3'O-methyl-epicatechin-O-β-glucuronide, quercetin-O-β-glucuronide, and O-methyl-quercetin-O-β-glucuronide were analyzed in plasma, urine, and regional brain extracts from AGSE groups. Anthocyanidin-O-galactosides and O-glucosides of delphinidin (Del), cyanidin (Cyn), petunidin (Pet), peonidin (Peo), and malvidin (Mal) were analyzed in plasma, urine, and brain extracts from bilberry groups.

Conclusion: Significant plasma dose-dependence was observed in flavan-3-ol metabolites of the AGSE group and in Mal, Del and Cyn galactosides and Pet, Peo, and Cyn glucosides of the bilberry groups. In the brain, a significant dose dependence was found in the cerebellum and frontal cortex in all major flavan-3-ol metabolites. All anthocyanidin glycosides, except for delphinidin, showed a dose-dependent increase in the cerebellum.
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http://dx.doi.org/10.1002/mnfr.201500224DOI Listing
December 2015

Reply: To PMID 24874999.

Am J Ophthalmol 2015 Feb;159(2):410-1

Los Angeles, California.

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http://dx.doi.org/10.1016/j.ajo.2014.11.014DOI Listing
February 2015

Thermal degradation of green tea flavan-3-ols and formation of hetero- and homocatechin dimers in model dairy beverages.

Food Chem 2015 Apr 15;173:305-12. Epub 2014 Oct 15.

Department of Food Science, Purdue University, 745 Agriculture Mall Dr., West Lafayette, IN 47906, USA; Department of Nutrition Science, Purdue University, 700 W. State St., West Lafayette, IN 47907, USA. Electronic address:

Interactions between polyphenols and macromolecules may impact polyphenol stability and bioavailability from foods. The impact of milk on tea flavan-3-ol stability to thermal treatment was investigated. Single strength (36.2 protein per L), quarter strength (9.0 g protein per L) milk, and control model beverages were incubated with epigallocatechin gallate and green tea extract at 62 or 37 °C for 180 min. Intact flavan-3-ols and select auto-oxidation products [theasinesins (THSNs) and P-2 dimers] were quantified by LC-MS. Generally, greater polyphenol to protein ratios increased first order degradation rates, consequently decreasing formation of oxidation products. The presence of galloyl and hydroxy moieties was associated with higher stability of monomeric flavan-3-ols with increasing protein concentrations suggesting potential for protein affinity to stabilise flavan-3-ols to thermal treatment. Absence of these moieties led to no observable improvements in stability. These results suggest that protein interactions may be useful in stabilising flavan-3-ols through thermal processing.
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http://dx.doi.org/10.1016/j.foodchem.2014.10.026DOI Listing
April 2015

New directions in the treatment of normal tension glaucoma.

Indian J Ophthalmol 2014 May;62(5):529-37

Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, USA.

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.
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http://dx.doi.org/10.4103/0301-4738.133481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065500PMC
May 2014

Bleb revision for resolution of hypotony maculopathy following primary trabeculectomy.

Am J Ophthalmol 2014 Sep 27;158(3):597-604.e1. Epub 2014 May 27.

Jules Stein Eye Institute, Department of Ophthalmology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California. Electronic address:

Purpose: To describe a surgical method of bleb revision for hypotony maculopathy, to evaluate its long-term efficacy, and to define the relationship between the duration of hypotony maculopathy and visual acuity (VA) outcomes.

Design: Noncomparative retrospective case series.

Methods: Medical records of 33 patients with hypotony maculopathy who underwent primary bleb revision between June 1999 and September 2012 by a single surgeon at an academic medical center were reviewed. Hypotony maculopathy was characterized by the presence of a decrease in VA, retinal striae, and macular edema in the setting of decreased intraocular pressure (IOP) after glaucoma filtering surgery. The main outcome measure was final logMAR VA after bleb revision at 6 and 12 months.

Results: Thirty-three eyes of 33 patients were followed for 4.68 ± 3.56 years (range 0.55-12.69 years). Mean duration of hypotony maculopathy was 4.98 ± 8.93 months. LogMAR VA improved from 0.78 ± 0.40 at baseline to 0.34 ± 0.34 (P < .001) 6 months after bleb revision and to 0.45 ± 0.55 (P < .001) 12 months after bleb revision. Spearman rank coefficient (rs) correlating duration of hypotony and BCVA at both 6 and 12 months was significant (P = .015 and rs = 0.426, P = .028 and rs = 0.416, respectively). Mean IOP increased from 3.51 ± 2.27 mm Hg to 12.06 ± 4.06 mm Hg (P < .001) at 12 months. Fifty-two percent were on no antiglaucoma medications at last follow-up. Five eyes (15%) required a second bleb revision to correct persistent hypotony maculopathy.

Conclusion: Surgical repair for hypotony maculopathy provided a significant improvement in VA at 6 and 12 months. Surgical bleb revision is associated with good long-term control of IOP and improved VA in eyes with hypotony maculopathy after previous glaucoma filtering surgery.
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http://dx.doi.org/10.1016/j.ajo.2014.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314713PMC
September 2014

Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model.

Mol Nutr Food Res 2013 Dec 21;57(12):2091-102. Epub 2013 Aug 21.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; New Use Agriculture and Natural Plant Products Program, Department of Plant Biology and Pathology, Rutgers University, New Brunswick, NJ, USA.

Scope: Metabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome.

Methods And Results: We found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity.

Conclusion: Our study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory.
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http://dx.doi.org/10.1002/mnfr.201300230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855562PMC
December 2013

Photo- and thermodegradation of anthocyanins from grape and purple sweet potato in model beverage systems.

J Agric Food Chem 2013 Feb 1;61(6):1364-72. Epub 2013 Feb 1.

Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47906, USA.

Recently, interest in the application of natural pigments to replace synthetic dyes in beverages has grown. The present study investigates the stability of anthocyanin-rich grape and purple sweet potato (PSP) extracts to photo- and thermostresses in ready-to-drink (RTD) beverage models including hot fill beverages with various concentrations of ascorbic acid, a preserved beverage, and a vitamin-enriched water beverage. Thermo- and photostresses were induced at 40, 60, and 80 °C and 250, 500, and 750 W/m(2), respectively. Qualitative and quantitative data on anthocyanin content were collected by pH differential assay and LC-MS. Increasing concentration of ascorbic acid caused more rapid degradation through thermostress, but had a protective effect through photostress. Additionally, PSP was significantly less stable than grape extract in the vitamin-enriched water model beverage through photostress. Furthermore, photostress caused the formation of monoacylated peonidins from diacylated peonidins.
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http://dx.doi.org/10.1021/jf3044007DOI Listing
February 2013

Assessment of phytochemical content in human milk during different stages of lactation.

Nutrition 2013 Jan;29(1):195-202

Department of Food Science, Purdue University, West Lafayette, Indiana, USA.

Objective: The present study reports the presence of several carotenoids and flavonoids in human milk samples.

Methods: Samples were collected from 17 women who delivered healthy term babies (≥ 37 wk of gestation) at 1-, 4-, and 13-wk postpartum intervals.

Results: Epicatechin (63.7-828.5 nmol/L), epicatechin gallate (55.7-645.6 nmol/L), epigallocatechin gallate (215.1-2364.7 nmol/L), naringenin (64.1-722.0 nmol/L), kaempferol (7.8-71.4 nmol/L), hesperetin (74.8-1603.1 nmol/L), and quercetin (32.5-108.6 nmol/L) were present in human milk samples with high inter-/intraindividual variability. With the exception of kaempferol, the mean flavonoid content in human milk was not statistically different among lactation stages. In contrast, carotenoids α-carotene (59.0-23.2 nmol/L), β-carotene (164.3-88.0 nmol/L), α-cryptoxanthin (30.6-13.5 nmol/L), β-cryptoxanthin (57.4-24.8 nmol/L), zeaxanthin (46.3-21.4 nmol/L), lutein (121.2-56.4 nmol/L), and lycopene (119.9-49.5 nmol/L) significantly decreased from weeks 1 to 13 of lactation.

Conclusion: The observed differences in the relative concentrations of the two phytochemical classes in human milk may be a result of several factors, including dietary exposure, stability in the milk matrix, efficiency of absorption/metabolism, and transfer from plasma to human milk. These data support the notion that flavonoids, as with carotenoids, are dietary phytochemicals present in human milk and potentially available to breast-fed infants.
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http://dx.doi.org/10.1016/j.nut.2012.07.015DOI Listing
January 2013

Bilateral vision loss responsive to corticosteroids.

Surv Ophthalmol 2013 Nov-Dec;58(6):634-9. Epub 2012 Nov 13.

Department of Ophthalmology, Harkness Eye Institute, Columbia University, New York, New York, USA.

A 48-year-old woman presented with painless bilateral vision loss that began in the left eye and responded to steroids, followed by vision loss in the right eye one day after completing her steroid taper. Diagnosis was complicated by a positive screening test for Leber hereditary optic neuropathy and a negative workup for demyelinating disease. Steroid-dependent optic neuropathies such as autoimmune optic neuropathy and chronic relapsing inflammatory optic neuropathy were considered in the differential. Seven months after initial presentation, the patient developed a new periventricular white matter lesion, lesions on her cervical and thoracic spinal cord, bilateral leg weakness, and sensory loss consistent with multiple sclerosis.
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http://dx.doi.org/10.1016/j.survophthal.2012.05.006DOI Listing
February 2014

DFPE, partially fluorinated ether: a novel approach for experimental intravitreal tamponade.

Retina 2013 Jan;33(1):120-7

Department of Ophthalmology, Columbia University/Harkness Eye Institute, New York, New York, USA.

Purpose: To evaluate decafluoro-di-n-pentyl ether (DFPE) as a vitreous tamponade by examining ocular tolerance in rabbits' eyes.

Methods: Thirteen rabbits were divided into 4 groups after mechanical vitrectomy and were followed up to 12 months. The tamponade remained in the eye for 6 months in group 1 (DFPE) and Group 3 (DFPE and silicone oil) and for 12 months in group 2 (DFPE). Group 4 served as control.

Results: In groups 1, 2, and 3, dispersion of the fluid appeared 2 weeks postoperatively. Posterior subcapsular cataracts appeared in rabbits' eyes with large fills of DFPE (>50%). Histologic findings in groups 1 and 2 showed no detectable change in outer nuclear layer thickness. Except for some vacuolations, the inner retina was well preserved in all injected rabbits' eyes. On the electroretinography of injected rabbits' eyes, there was no effect on the a wave amplitude and b wave implicit time, but the b wave amplitude was elevated with statistical significance (P < 0.001) at 1, 3, and 6 months postoperatively but with no statistical significance (P > 0.05) after that period when compared with group 4 and unoperated fellow rabbits' eyes of each group.

Conclusion: Decafluoro-di-n-pentyl ether demonstrated minimum adverse effects in retinal rabbits; further studies are needed before clinical use as short-term tamponade.
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http://dx.doi.org/10.1097/IAE.0b013e31825db6cfDOI Listing
January 2013

Aqueous vascular endothelial growth factor and endothelin-1 levels in branch retinal vein occlusion associated with normal tension glaucoma.

J Glaucoma 2013 Feb;22(2):104-9

Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Seoul, South Korea.

Purpose: To evaluate aqueous levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in patients with branch retinal vein occlusion (BRVO) with and without normal tension glaucoma (NTG), and to assess the therapeutic efficacy of intravitreal bevacizumab (IVB) in these patients.

Methods: Sixteen eyes with NTG of 48 age and sex-matched eyes without NTG that had previously received IVB for BRVO were followed for 6 months. Aqueous VEGF and ET-1 levels were measured by enzyme-linked immunosorbent assay at the time of baseline IVB. Logarithm of the minimum angle of resolution best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and then at 1, 3, and 6 months postinjection.

Results: The obstruction site of BRVO was closer to the optic disk in eyes with NTG compared with controls (P=0.001). Baseline BCVA, CMT, and VEGF levels were similar between the 2 groups. Baseline ET-1 levels were significantly higher in eyes with NTG than those without NTG (P=0.009). After IVB, there was a significant improvement in both BCVA and CMT at 6 months, irrespective of the presence of NTG. However, BCVA in the presence of NTG was significantly worse at 6 months compared with eyes without NTG even though CMT was similarly reduced in both groups (P=0.04).

Conclusions: Aqueous VEGF levels are similar in patients with BRVO with or without NTG, whereas aqueous ET-1 levels are elevated in the presence of NTG. Although IVB may be effective in the treatment of BRVO, the presence of NTG may limit visual recovery despite anatomic recovery of CMT.
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http://dx.doi.org/10.1097/IJG.0b013e3182312047DOI Listing
February 2013

Tea catechin auto-oxidation dimers are accumulated and retained by Caco-2 human intestinal cells.

Nutr Res 2010 May;30(5):327-40

Department of Food Science, Purdue University, West Lafayette, IN 47907, USA.

Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 mumol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 mumol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% +/- 0.28% and 1.53% +/- 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% +/- 2.1% and 10.1% +/- 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% +/- 2.2% and 4.65% +/- 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% +/- 22% and 29.6% +/- 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium.
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http://dx.doi.org/10.1016/j.nutres.2010.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929646PMC
May 2010

Intravitreal recombinant human erythropoietin: a safety study in rabbits.

Curr Eye Res 2008 Sep;33(9):750-60

Brown Glaucoma Research Laboratory, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Purpose: To evaluate the ocular safety of varying doses of a single intravitreal injection of the candidate neuroprotective agent, recombinant human erythropoietin (rhEPO).

Methods: Thirty New Zealand rabbits were divided into one of six groups: untreated controls, intravitreal saline injection, and intravitreal injections of rhEPO (100 U, 250 U, 500 U, or 1000 U). Electroretinography (ERG) was performed one day prior to injection and on post-injection days 3, 7, 14, and 21. Fluorescein angiography was done on post-injection day 28 and graded for the presence of neovascularization by a masked observer. Animals were sacrificed for histologic examination 30 days after injection.

Results: Except for the rhEPO 500 U group on day 21, there were no statistically significant differences in the amplitude or implicit time of the ERGs between groups or at different timepoints. Fluorescein angiography showed no evidence of neovascularization. Light microscopy showed no apparent abnormalities in retinal morphology or evidence of retinal damage compared to control groups.

Conclusion: A single 0.1-ml intravitreal injection of rhEPO at a dose of up to 1000 U does not appear to cause adverse effects on retinal vasculature, retinal anatomy, or ERG function in albino rabbits.
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http://dx.doi.org/10.1080/02713680802366602DOI Listing
September 2008

Hemorrhagic complications from glaucoma surgery in patients on anticoagulation therapy or antiplatelet therapy.

Am J Ophthalmol 2008 Apr 6;145(4):736-746. Epub 2008 Feb 6.

Jules Stein Eye Institute, UCLA, Los Angeles, California 90095, USA.

Purpose: To determine the incidence of and risk factors for hemorrhagic complications in patients on anticoagulation (ACT) or antiplatelet therapy (APT) having glaucoma surgery.

Design: Retrospective case-control study.

Methods: Medical records of patients who had glaucoma surgery between July 1, 1998 and March 31, 2005 were reviewed. Patients who either used ACT/APT continuously throughout the perioperative period or discontinued its use prior to surgery were compared to case-matched control patients who were not on such therapies. Patients on ACT/APT who experienced postoperative hemorrhagic complications were compared to those who did not. Outcome measures included hemorrhagic complications and thromboembolic events.

Results: Three hundred and forty-seven patients (eyes) who were on ACT or APT prior to glaucoma surgery had a higher rate of hemorrhagic complications than 347 control patients (10.1% vs 3.7%, respectively, P = .002). Patients on ACT had a higher rate of hemorrhagic complications than patients on APT (22.9% vs 8.0%, respectively, P = .003). Patients who continued ACT during glaucoma surgery had the highest rate of hemorrhagic complications (31.8%) when compared to patients who discontinued ACT prior to surgery or patients who used APT alone (P = .001). Hemorrhagic complications following glaucoma surgery were more frequently associated with preoperative ACT, arrhythmia, and higher preoperative and postoperative intraocular pressures (IOP).

Conclusion: Chronic ACT/APT was associated with a statistically significant increase in the rate of hemorrhagic complications, and perioperative ACT and a high preoperative IOP are potential risk factors for hemorrhagic complications in patients undergoing glaucoma surgery.
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http://dx.doi.org/10.1016/j.ajo.2007.12.007DOI Listing
April 2008

Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma.

J Glaucoma 2007 Sep;16(6):567-71

Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06520-8061, USA.

Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue-protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials.
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http://dx.doi.org/10.1097/IJG.0b013e318156a556DOI Listing
September 2007

Feasibility and efficacy of a mass switch from latanoprost to bimatoprost in glaucoma patients in a prepaid Health Maintenance Organization.

Ophthalmology 2005 Dec 12;112(12):2123-30. Epub 2005 Oct 12.

Jules Stein Eye Institute, University of California, Los Angeles, California 90095, USA.

Objective: To assess the feasibility of an automatic switch of a large number of patients with glaucoma or suspicion of glaucoma from latanoprost to bimatoprost, and to compare the efficacy of the 2 prostaglandin analogs before and after the switch.

Design: Retrospective nonrandomized comparison.

Participants: Forty-three thousand four hundred forty-one California patients and 538 patients at one Southern California clinical facility of a nationwide prepaid health maintenance organization (HMO) who were on either prostaglandin between March 2002 and December 2003 (21 months).

Methods: Beginning in April 2002, patients on latanoprost were systemically switched to bimatoprost by the HMO pharmacy service after obtaining approval from the entire ophthalmology staff. PART 1: computerized dispensing records of California patients were retrieved. PART 2: medical records of patients at one clinical facility were reviewed.

Main Outcome Measures: Rates of switching or switching back from one prostaglandin to another, intraocular pressure (IOP) control, and intolerability.

Results: PART 1: 17847 patients initially received latanoprost. Of them, 84.8% were switched from latanoprost to bimatoprost, and 13.0% were switched back to latanoprost. Twenty-five thousand five hundred ninety-four patients were started on bimatoprost without previous experience with latanoprost. Of them, 8.6% were later switched to latanoprost use instead. Patients who had previous experience with latanoprost had a statistically significantly higher rate of switching back to latanoprost after a period of bimatoprost use when compared with those who had no prior experience with latanoprost (13.0% vs. 8.6%, respectively; P<0.0001). PART 2: 309 patients were switched from latanoprost to bimatoprost. The mean IOP reduction of 0.51+/-2.77 mmHg (95% confidence interval, 0.20-0.82) after the switch was statistically significant (P = 0.001). Forty-one patients (13.3%) had a decrease of >3 mmHg of IOP. The statistical significance of the IOP reduction after the switch remains in the monotherapy group (P = 0.005) but not in the multitherapy group (P = 0.058). Thirty-three patients (10.7%) who were switched from latanoprost to bimatoprost discontinued bimatoprost and resumed latanoprost.

Conclusion: A systematic pharmacy-level switch from latanoprost to bimatoprost in a nationwide HMO achieved a high switch rate, with little switching back. There was a small but statistically significant reduction in mean IOP after the switch. An appreciable proportion of patients switched had a clinically significant reduction of IOP.
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http://dx.doi.org/10.1016/j.ophtha.2005.06.031DOI Listing
December 2005

Lead exposure and cataract risk in men.

Authors:
Brian J Song

JAMA 2005 Apr;293(14):1724; author reply 1724-5

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http://dx.doi.org/10.1001/jama.293.14.1724-bDOI Listing
April 2005