Publications by authors named "Glenn Yiu"

79 Publications

Research Funding, Income, and Career Satisfaction among Clinician-Scientists in Ophthalmology in the United States.

Am J Ophthalmol 2021 Apr 6. Epub 2021 Apr 6.

Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento. Electronic address:

Purpose: To characterize clinician-scientists in ophthalmology and identify factors associated with successful research funding, income, and career satisfaction.

Design: Cross-sectional study METHODS: We conducted a survey of clinician-scientists in ophthalmology at U.S. academic institutions between April 17, 2019 and May 19, 2019. We collected information including 1) demographic data, 2) amount, type, and source of startup funding, first extramural grant, and first R01-equivalent independent grant, 3) starting and current salaries, and 4) Likert-scale measures of career satisfaction were analyzed using multivariate regression.

Results: 98 clinician-scientists in ophthalmology were surveyed across different ages (mean 48±11 years), research categories, institutional types, geographic regions, and academic ranks. Median startup funding was $50-99k, and median starting salary was $150-199k. Most investigators (67%) received their first extramural award from the National Eye Institute, mostly through K-award mechanisms (82%). The median time to receiving their first independent grant was 8 years, mostly through an R01 award (70%). Greater institutional startup support (P=0.027) and earlier extramural grant success (P=0.022) were associated with earlier independent funding. Male gender (P = 0.001) and MD degree (P=0.008) were associated with higher current salaries, but not starting salaries. Overall career satisfaction increased with career duration (P=0.011), but not with earlier independent funding (P=0.746) or higher income (P=0.300).

Conclusions: Success in research funding by clinician-scientists in ophthalmology may be linked to institutional support and earlier acquisition of extramural grants, but does not impact academic salaries. Nevertheless, career satisfaction among clinician-scientists improves with time, which is not necessarily influenced by research or financial success.
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http://dx.doi.org/10.1016/j.ajo.2021.03.034DOI Listing
April 2021

Natural History and Predictors of Vision Loss in Eyes with Diabetic Macular Edema and Good Initial Visual Acuity.

Retina 2021 Mar 9. Epub 2021 Mar 9.

Department of Ophthalmology and Vision Science, University of California Davis, 4860 Y Street Suite 2400, Sacramento, CA, 95817, United States California Northstate University College of Medicine, 9700 W Taron Drive, Elk Grove, CA, 95757, United States University of Nevada, Reno School of Medicine, 1664 North Virginia Street, Reno, NV 89557-0357, United States Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, United States Department of Public Health Sciences/Division of Biostatistics, University of California Davis, 1 Shields Ave, Davis, CA, 95616, United States.

Purpose: To identify clinical and anatomic factors associated vision loss in eyes with treatment-naïve diabetic macular edema (DME) and good initial visual acuity (VA).

Methods: Retrospective cohort study following long-term history of eyes with untreated center-involving DME and baseline VA ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007-March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, VA, and diabetic retinopathy (DR) severity; and spectral domain-optical coherence tomography (SD-OCT) biomarkers including central subfield thickness (CST),intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy.

Results: 56 eyes (48 patients) with untreated DME and mean baseline VA of logMAR 0.05 ± 0.05 (Snellen 20/22) was followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio (HR) 1.04/year, P=0.0195), and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative DR (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the SD-OCT cyst diameter (HR 1.0, P = 0.0094).

Conclusions: In eyes with DME and good initial vision, those with older age and worse DR severity should be monitored closely for prompt treatment initiation when vision loss occurs.
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http://dx.doi.org/10.1097/IAE.0000000000003167DOI Listing
March 2021

Patterns and Predictors of Successful Treatment Discontinuation in Retinal Vein Occlusions With Macular Edema in the Real World.

Ophthalmic Surg Lasers Imaging Retina 2021 Feb;52(2):84-92

Background And Objective: To identify factors associated with successful treatment discontinuation in eyes with retinal vein occlusions (RVOs) and macular edema (ME) in real-world settings.

Patients And Methods: Retrospective study of 214 eyes with RVO and ME with 24-month follow-up at five academic centers. Regression analyses identified factors associated with (1) successful treatment discontinuation for at least 6 months without fluid recurrence and (2) best-corrected visual acuity (BCVA) at 24 months.

Results: Forty percent of eyes with branch RVO and 35% with central RVO (CRVO) / hemi-retinal RVO (HRVO) successfully discontinued therapy without fluid recurrence, with median time to discontinuation of 6 and 7 months, respectively. Lower 6-month central subfield thickness was associated with greater likelihood of treatment discontinuation within 24 months for eyes with CRVO/HRVO (P = .001), whereas better 6-month BCVA was associated with better 24-month BCVA for all RVO subtypes (P < .001).

Conclusion: Early anatomic response at 6 months is associated with greater likelihood of stopping treatments. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:84-92.].
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http://dx.doi.org/10.3928/23258160-20210201-05DOI Listing
February 2021

3-Dimensional Visualization of Arteriovenous Crossing in a Branch Retinal Vein Occlusion.

Ophthalmology 2021 Mar;128(3):363

Department of Ophthalmology and Vision Science, UC Davis, Sacramento, California.

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http://dx.doi.org/10.1016/j.ophtha.2020.09.035DOI Listing
March 2021

Identification of Patients with Pentosan Polysulfate Sodium-Associated Maculopathy through Screening of the Electronic Medical Record at an Academic Center.

J Ophthalmol 2020 17;2020:8866961. Epub 2020 Dec 17.

Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA, USA.

Aims: This chart review of a quaternary academic medical center electronic medical record (EMR) aimed to identify patients at risk of development of maculopathy with exposure to pentosan polysulfate sodium (PPS).

Methods: A review of electronic medical records of a quaternary medical center of patients with either documented exposure to PPS or diagnosis of interstitial cystitis (IC) from 2007 to 2019 was performed for retinal imaging and visual acuity; the study was conducted in August of 2019.

Results: 216 charts were included for analysis, of which 96 had documented eye exams and 24 had retinal imaging done. We identified three patients with maculopathy in the context of long-term exposure to PPS via chart review, and one additional patient was identified by referral. The median PPS exposure duration was 11 years (range 7 to 19 years). Median logMAR BCVA OD 0.6 range was 0.0-1.9 (approximate Snellen equivalent 20/80 range (20/20-20/1600)) and OS 0.7 range was 0.1-1.9 (approximate Snellen equivalent 20/100 range (20/25-20/1600)). Ultrawidefield color fundus imaging and fundus autofluorescence revealed findings of pigmentary changes and patchy macular atrophy. Optical coherence tomography (OCT) demonstrated outer retinal thinning and increased choroidal transmission coincident with areas of atrophy seen on fundus imaging.

Conclusions: Less than half of patients at risk for development of maculopathy due to exposure to PPS had received eye examinations, suggesting that those at risk are not receiving adequate screening. We found two patients with PPS maculopathy who had relatively preserved central vision, one patient with bitemporal vision loss, and one patient who developed vision loss in both eyes.
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http://dx.doi.org/10.1155/2020/8866961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803106PMC
December 2020

Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes.

Hum Gene Ther 2021 Apr 8. Epub 2021 Apr 8.

Department of Cell Biology and Human Anatomy, University of California Davis, Davis, California, USA.

The suprachoroid is a potential space located between the sclera and choroid of the eye, which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of adeno-associated virus (AAV)8 using transscleral microneedles enables widespread transgene expression in eyes of nonhuman primates, but may cause intraocular inflammation. We characterized the host humoral and cellular immune responses after suprachoroidal delivery of AAV8 expressing green fluorescent protein (GFP) in rhesus macaques, and found that it can induce mild chorioretinitis that resolves after systemic corticosteroid administration, with recovery of photoreceptor morphology, but persistent immune cell infiltration after 3 months, corresponding to a loss of GFP expression from retinal pigment epithelial cells, but persistent expression in scleral fibroblasts. Suprachoroidal AAV8 triggered B cell and T cell responses against GFP, but only mild antibody responses to the viral capsid compared to intravitreal injections of the same vector and dose. Systemic biodistribution studies showed lower AAV8 levels in liver and spleen after suprachoroidal injection compared with intravitreal delivery. Our findings suggest that suprachoroidal AAV8 primarily triggers host immune responses to GFP, likely due to sustained transgene expression in scleral fibroblasts outside the blood-retinal barrier, but elicits less humoral immune reactivity to the viral capsid than intravitreal delivery due to lower egress into systemic circulation. As GFP is not native to primates and not a clinically relevant transgene, suprachoroidal AAV delivery of human transgenes may have significant translational potential for retinal gene therapy.
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http://dx.doi.org/10.1089/hum.2020.281DOI Listing
April 2021

Anti-Retinal Antibodies in Vitamin A Deficiency.

Ophthalmic Surg Lasers Imaging Retina 2020 12;51(12):723-726

Vitamin A is an important component of the visual cycle, and its deficiency causes a retinal degeneration that may be reversed with retinol supplementation. Here, the authors present a patient with vitamin A deficiency and rod-mediated retinopathy who was found to have multiple anti-retinal antibodies that gradually dissipated after vitamin A supplementation. This interesting case suggests the possibility that the photoreceptor degeneration induced by vitamin A deficiency may lead to transient immune exposure to retinal antigens and development of anti-retinal antibodies. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:723-726.].
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http://dx.doi.org/10.3928/23258160-20201202-07DOI Listing
December 2020

Evolution of ocular defects in infant macaques following in utero Zika virus infection.

JCI Insight 2020 12 17;5(24). Epub 2020 Dec 17.

California National Primate Research Center, Davis, California, USA.

Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood-retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.
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http://dx.doi.org/10.1172/jci.insight.143947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819741PMC
December 2020

Visible light OCT improves imaging through a highly scattering retinal pigment epithelial wall.

Opt Lett 2020 Nov;45(21):5945-5948

Here we provide a counter-example to the conventional wisdom in biomedical optics that longer wavelengths aid deeper imaging in tissue. Specifically, we investigate visible light optical coherence tomography of Bruch's membrane (BM) in the non-pathologic eyes of humans and two mouse strains. Surprisingly, we find that shorter visible wavelengths improve the visualization of BM in pigmented eyes, where it is located behind a highly scattering layer of melanosomes in the retinal pigment epithelium (RPE). Monte Carlo simulations of radiative transport suggest that, while absorption and scattering are higher at shorter wavelengths, detected multiply scattered light from the RPE is preferentially attenuated relative to detected backscattered light from the BM.
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http://dx.doi.org/10.1364/OL.405398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864585PMC
November 2020

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model.

Transl Vis Sci Technol 2020 02 27;9(3):30. Epub 2020 Feb 27.

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California -Davis, Davis, CA, USA.

Purpose: To evaluate the safety and tolerability of a microsphere thermo-responsive hydrogel drug delivery system (DDS) loaded with aflibercept in a nonhuman primate model.

Methods: A sterile 50 µL of aflibercept-loaded microsphere thermo-responsive hydrogel-DDS (aflibercept-DDS) was injected intravitreally into the right eye of 10 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP) measurement, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram were performed monthly for 6 months. One macaque was euthanized monthly, and the enucleated eyes were submitted for measurement of bioactive aflibercept concentrations. Four eyes were submitted for histopathology.

Results: Injected aflibercept-DDS was visualized in the vitreous until 6 months postinjection. No abnormalities were observed in the anterior segment, and IOP remained within normal range during the study period. A small number of cells were observed in the vitreous of some macaques, but otherwise the remainder of the posterior segment examination was normal. No significant changes in retinal architecture or function as assessed by SD-OCT and histology or full-field electroretinography, respectively, were observed. A mild, focal foreign body reaction around the injectate was observed with histology at 6 months postinjection. A mean of 2.1 ng/µL of aflibercept was measured in the vitreous.

Conclusions: Intravitreally injected aflibercept-DDS achieved controlled, sustained release of aflibercept with no adverse effects for up to 6 months in the eyes of healthy rhesus macaques.

Translational Relevance: Aflibercept-DDS may be a more effective method to deliver bioactive antivascular endothelial growth factor agents than current practice by reducing the frequency of intravitreal injections and providing controlled drug release.
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http://dx.doi.org/10.1167/tvst.9.3.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354880PMC
February 2020

Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.

Invest Ophthalmol Vis Sci 2020 07;61(8):16

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Purpose: To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD).

Methods: The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis.

Results: Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001).

Conclusions: In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.
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http://dx.doi.org/10.1167/iovs.61.8.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425688PMC
July 2020

Cost Analysis of Teleophthalmology Screening for Diabetic Retinopathy Using Teleophthalmology Billing Codes.

Ophthalmic Surg Lasers Imaging Retina 2020 05;51(5):S26-S34

Background And Objective: To evaluate the financial sustainability of teleophthalmology screening for diabetic retinopathy (DR) using telehealth billing codes.

Patients And Methods: The authors performed an Institutional Review Board-approved retrospective review of medical records, billing data, and quality metrics at the University of California Davis Health System from patients screened for DR through an internal medicine-based telemedicine program using CPT codes 92227 or 92228.

Results: A total of 290 patients received teleophthalmology screening over a 12-month period, resulting in an increase in the DR screening rate from 49% to 63% (P < .0001). The average payment per patient was $19.86, with an estimated cost of $41.02 per patient. The projected per-patient incentive bonus was $43.06 with a downstream referral revenue of $39.38 per patient. One hundred seventy-eight clinic visits were eliminated, providing an estimated cost savings of $42.53 per patient.

Conclusion: Sustainable teleophthalmology screening may be achieved by billing telehealth codes but only with health care incentive bonuses, patient referrals, and by accounting for the projected cost-savings of eliminating office visits. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S26-S34.].
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http://dx.doi.org/10.3928/23258160-20200108-04DOI Listing
May 2020

Drusen in dense deposit disease: not just age-related macular degeneration.

Lancet 2020 05;395(10238):1726

Department of Ophthalmology and Vision Science, University of California, Davis, Sacramento, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)30976-4DOI Listing
May 2020

Asymmetry in Pigmented Paravenous Retinochoroidal Atrophy.

JAMA Ophthalmol 2020 03 12;138(3):e190911. Epub 2020 Mar 12.

Department of Ophthalmology & Vision Sciences,University of California, Davis, Sacramento.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.0911DOI Listing
March 2020

Factors Impacting Efficacy of AAV-Mediated CRISPR-Based Genome Editing for Treatment of Choroidal Neovascularization.

Mol Ther Methods Clin Dev 2020 Jun 23;17:409-417. Epub 2020 Jan 23.

Department of Ophthalmology & Vision Science, University of California, Davis, Davis, CA, USA.

Frequent injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a clinical burden for patients with neovascular age-related macular degeneration (AMD). Genomic disruption of using adeno-associated viral (AAV) delivery of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 has the potential to permanently suppress aberrant angiogenesis, but the factors that determine the optimal efficacy are unknown. Here, we investigate two widely used Cas9 endonucleases, SpCas9 and SaCas9, and evaluate the relative contribution of AAV-delivery efficiency and genome-editing rates to determine the mechanisms that drive successful CRISPR-based suppression of VEGF-A, using a mouse model of laser-induced choroidal neovascularization (CNV). We found that SpCas9 demonstrated higher genome-editing rates, greater VEGF reduction, and more effective CNV suppression than SaCas9, despite similar AAV transduction efficiency between a dual-vector approach for SpCas9 and single-vector system for SaCas9 to deliver the Cas9 orthologs and single guide RNAs (gRNAs). Our results suggest that successful VEGF knockdown using AAV-mediated CRISPR systems may be determined more by the efficiency of genome editing rather than viral transduction and that SpCas9 may be more effective than SaCas9 as a potential therapeutic strategy for CRISPR-based treatment of CNV in neovascular AMD.
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http://dx.doi.org/10.1016/j.omtm.2020.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044682PMC
June 2020

Long-term Evolution and Remodeling of Soft Drusen in Rhesus Macaques.

Invest Ophthalmol Vis Sci 2020 02;61(2):32

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Purpose: To characterize the evolution and structure of soft drusen in aged rhesus macaques using in vivo multimodal retinal imaging and ex vivo histologic and ultrastructural analyses as a nonhuman primate model of early age-related macular degeneration (AMD).

Methods: Multimodal imaging including fundus photography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were used to characterize and track individual drusen lesions in 20 aged rhesus macaques (mean age 23.3 ± 2.7 years) with drusenoid lesions over 2 years, followed by semithin histologic analysis and transmission electron microscopy (TEM).

Results: Although most drusen gradually increased in size, a portion spontaneously regressed or collapsed over 2 years. Histologic analyses showed that soft drusen exhibit hypertrophy and dysmorphia of overlying retinal pigment epithelium (RPE), as seen in early and intermediate AMD, but do not exhibit RPE atrophy, RPE migration, or photoreceptor degeneration characteristic of advanced AMD. Ultrastructure of soft drusen showed abundant lipid particles within Bruch's membrane and AMD-related basal linear deposits (BlinD) resembling those in human drusen.

Conclusions: The dynamic remodeling, histologic findings, and ultrastructural features of soft drusen in aged rhesus macaques support nonhuman primates as an animal model of early AMD and reveal important insights into drusen biogenesis and AMD development.
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http://dx.doi.org/10.1167/iovs.61.2.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326602PMC
February 2020

Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Mol Ther Methods Clin Dev 2020 Mar 21;16:179-191. Epub 2020 Jan 21.

Clearside Biomedical, 900 North Point Parkway, Suite 200, Alpharetta, GA 30005, USA.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier.
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http://dx.doi.org/10.1016/j.omtm.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005511PMC
March 2020

Retinal Vessel Density in Exudative and Nonexudative Age-Related Macular Degeneration on Optical Coherence Tomography Angiography.

Am J Ophthalmol 2020 04 16;212:7-16. Epub 2019 Dec 16.

Department of Ophthalmology and Vision Science, University of California, Davis, Sacramento, California. Electronic address:

Purpose: Although the choroid contributes to the pathogenesis of age-related macular degeneration (AMD), the role of retinal perfusion is unclear. We sought to compare retinal vascular measurements between eyes with nonexudative and exudative AMD using optical coherence tomography angiography (OCT-A).

Design: Retrospective, cross-sectional study.

Methods: OCT-A images were analyzed from 310 eyes of 182 patients (mean age ± standard deviation [SD], 78.8 ± 8.8 years) with nonexudative (54.2%) and exudative (45.8%) AMD to measure retinal vessel density (VD) from the superficial capillary plexus in the foveal, parafoveal, and full macular regions and foveal avascular zone (FAZ) area, perimeter, and circularity. Multivariate regressions were used to compare nonexudative and exudative AMD eyes and the impact of anti-vascular endothelial growth factor (anti-VEGF) treatments or geographic atrophy (GA).

Results: In eyes with AMD, VD decreases with age in the foveal (β = -0.211, P < .001), parafoveal (β = -0.305, P < .001), and full macular regions (β = -0.295, P < .001). Eyes with exudative AMD demonstrated lower VD, especially in the parafoveal (29.8% ± 6.3% vs 33.0% ± 5.7%, P < .001) and full regions (27.9% ± 6.2% vs 31.2% ± 5.5%, P < .001) compared with nonexudative AMD. There were no differences in FAZ area, perimeter, or circularity between the 2 groups (P = .503-.907). In eyes with exudative AMD, previous anti-VEGF treatments did not impact retinal vascular measurements (P = .324-.986). Nonexudative AMD severity and presence of central GA also impacted retinal VD and FAZ morphology.

Conclusions: Retinal VD is decreased in eyes with exudative AMD compared with nonexudative AMD but is unaffected by anti-VEGF treatments, suggesting a retinal vascular contribution to the pathogenesis of AMD.
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http://dx.doi.org/10.1016/j.ajo.2019.11.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113105PMC
April 2020

Emerging Concepts in the Treatment of Diabetic Retinopathy.

Curr Diab Rep 2019 11 20;19(11):137. Epub 2019 Nov 20.

Department of Ophthalmology and Vision Science, University of California Davis, 4860 Y Street Suite 2400, Sacramento, CA, 95817, USA.

Purpose Of Review: Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults in the developed world. This review discusses the current approach to managing the disease, such as glycemic and blood pressure control, as well as laser photocoagulation, as well as emerging concepts and controversies on novel therapies.

Recent Findings: In recent years, the rise of intraocular anti-angiogenesis treatments is changing the paradigm of classic laser photocoagulation in the management of DR, but its long-term benefits remain an area of controversy. We also discuss new targets including anti-inflammation, neuroprotection, and novel laser technologies. Finally, we discuss new advances in retinal imaging that has vastly improved the diagnosis and management of DR. Diagnosis and management of diabetic retinopathy is a rapidly progressing field. Emerging concepts in ophthalmic imaging, medical treatments, and surgical approaches provide insights into how DR management will evolve in the near future.
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http://dx.doi.org/10.1007/s11892-019-1276-5DOI Listing
November 2019

Man in His 90s With a History of Tachycardia and Abnormal Findings on Slitlamp Examination of the Cornea.

JAMA Cardiol 2020 01;5(1):102

Department of Ophthalmology and Vision Science, University of California, Davis, Sacramento.

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http://dx.doi.org/10.1001/jamacardio.2019.4363DOI Listing
January 2020

CONVERSION AND SPONTANEOUS REVERSION OF LAMELLAR HOLE FROM FULL-THICKNESS MACULAR HOLE.

Retin Cases Brief Rep 2019 Nov 13. Epub 2019 Nov 13.

Department of Ophthalmology & Vision Science, University of California, Davis Health, Sacramento, California.

Purpose: To report the conversion and spontaneous reversion of a lamellar hole from full-thickness macular hole after vitrectomy surgery for retinal detachment repair.

Methods: Case report of a patient with a preexisting lamellar hole who underwent retinal detachment repair.

Results: A patient with a history of a lamellar hole developed a fovea-sparing retinal detachment that was repaired by vitrectomy surgery with gas tamponade. Two months after the surgery, he developed a full-thickness macular hole that spontaneously reverted back to a lamellar hole configuration over several months.

Conclusion: Although spontaneous closure of full-thickness macular hole after retinal detachment repair has been reported, the conversion and spontaneous reversion of a lamellar hole from full-thickness macular hole after vitrectomy provide insight into the tractional forces involved in the pathophysiology of lamellar and full-thickness macular holes.
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http://dx.doi.org/10.1097/ICB.0000000000000940DOI Listing
November 2019

Spectral-Domain OCT Predictors of Visual Outcomes after Ranibizumab Treatment for Macular Edema Resulting from Retinal Vein Occlusion.

Ophthalmol Retina 2020 01 28;4(1):67-76. Epub 2019 Aug 28.

Genentech, Inc, San Francisco, California.

Purpose: To evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE).

Design: Post hoc analysis of prospective clinical trial data.

Participants: Two hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema.

Methods: Baseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections.

Main Outcome Measures: Association of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections.

Results: Before therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001).

Conclusions: Although SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.
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http://dx.doi.org/10.1016/j.oret.2019.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944743PMC
January 2020

Real-world management and long-term outcomes of diabetic macular oedema with good visual acuity.

Eye (Lond) 2020 06 28;34(6):1108-1115. Epub 2019 Oct 28.

Department of Ophthalmology & Vision Sciences, University of California, Davis, Sacramento, CA, USA.

Purpose: To evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings.

Methods: We reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes.

Results: At presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 μm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P < 0.001) and earlier timing (P = 0.017) at initial treatment, but not CST at first treatment (P = 0.634) or cumulative number of injections or lasers (P = 0.441-0.606).

Conclusion: DMO with good initial visual acuity should be monitored closely, as delay in treatment initiation is associated with worse visual outcomes. BCVA at time of initial treatment is the strongest determinant of final visual acuity.
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http://dx.doi.org/10.1038/s41433-019-0647-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253473PMC
June 2020

Posterior Segment Complications and Impact on Long-Term Visual Outcomes in Eyes With a Type 1 Boston Keratoprosthesis.

Cornea 2019 Sep;38(9):1111-1116

Department of Ophthalmology and Vision Science, School of Medicine, University of California, Sacramento, CA.

Purpose: To determine the spectrum of retinal complications (RCs) in a cohort of eyes with a type 1 Boston keratoprosthesis (KPro).

Methods: All patients (36 eyes of 31 patients) who received a type 1 Boston KPro from January 2004 to December 2015 at the University of California, Davis, were included. Electronic medical records were reviewed for relevant clinical data. Demographic information, initial corneal diagnosis, postoperative course, posterior segment complications, preoperative and final visual acuity were tabulated and analyzed.

Results: Posterior segment complications after type 1 Boston KPro were identified in 56% of eyes (n = 20). They included retinal detachment (n = 11; 31%), retroprosthetic membrane (n = 10; 28%), endophthalmitis (n = 7; 19%), cystoid macular edema (n = 5; 14%), epiretinal membrane (n = 4; 11%), vitreous hemorrhage (n = 2; 6%), choroidal detachment (n = 2; 6%), retinal vein occlusion (n = 1; 3%), and macular hole (n = 1; 3%). During the average follow-up period of 53.8 months (median, 57.1 months; range, 1.8-108.7 months) after type 1 Boston KPro, final best-corrected visual acuity improved by a mean of 0.12 logarithm of the minimum angle of resolution (LogMAR) units (range, -2.26 to +2.26) overall. The proportion of eyes with final best-corrected visual acuity better than 20/200 was 2 of 20 (10%) in the group with RCs, in contrast to 7 of 16 eyes (44%) noted among eyes without RCs.

Conclusions: Long-term visual outcomes in eyes after type 1 Boston KPro may depend, in part, on maintaining a healthy posterior pole. Retinal detachment, in particular, may represent a threat to ultimate visual functioning. Regular examination of the peripheral fundus is recommended.
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http://dx.doi.org/10.1097/ICO.0000000000001983DOI Listing
September 2019

Inverted Hypopyon.

JAMA Ophthalmol 2019 Jun 13;137(6):e185256. Epub 2019 Jun 13.

Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.5256DOI Listing
June 2019

Choriovitreal Neovascularization After Resolution of Infectious Chorioretinitis.

Retina 2019 06;39(6):e21-e22

Department of Ophthalmology and Vision Science, University of California, Davis, California.

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http://dx.doi.org/10.1097/IAE.0000000000002558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534460PMC
June 2019

Statistical Issues on Evaluating Association Between the Cilioretinal Artery and Age-Related Macular Degeneration-Reply.

JAMA Ophthalmol 2019 07;137(7):856

Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.1115DOI Listing
July 2019

Long-term natural history of idiopathic epiretinal membranes with good visual acuity.

Eye (Lond) 2019 05 19;33(5):714-723. Epub 2019 Apr 19.

Department of Ophthalmology & Vision Sciences, University of California, Davis, Sacramento, CA, USA.

Background/objectives: To evaluate the long-term progression of idiopathic epiretinal membranes (iERMs) with good baseline visual acuity, and to identify predictors of visual decline.

Design: Retrospective case series SUBJECTS METHODS: We reviewed records of 145 eyes with iERM and best-corrected visual acuity (BCVA) of 20/40 or greater at presentation, including BCVA, lens status, and central macular thickness (CMT) at yearly visits; as well as anatomic biomarkers including vitreomacular adhesion, pseudohole, lamellar hole, intraretinal cysts, disorganization of the inner retinal layers (DRIL), and disruption of outer retinal layers. Linear mixed effects and mixed-effects Cox proportional hazards models were used to identify clinical and anatomic predictors of vision change and time to surgery.

Results: At presentation, mean BCVA was 0.17 ± 0.10 logMAR units (Snellen 20/30) and mean CMT was 353.3 ± 75.4 μm. After a median follow-up of 3.7 years (range 1-7 years), BCVA declined slowly at 0.012 ± 0.003 logMAR units/year, with phakic eyes declining more rapidly than pseudophakic eyes (0.019 ± 0.003 vs. 0.010 ± 0.004 logMAR units/year). Metamorphopsia, phakic lens status, lamellar hole, and inner nuclear layer cysts were associated with faster visual decline. Cumulative rates of progression to surgery were 2.9, 5.6, 12.2, and 21.1% at years 1-4. Visual symptoms, metamorphopsia, greater CMT, and disruption of outer retinal layers were associated with greater hazard for surgery.

Conclusion: Eyes with iERM and visual acuity ≥ 20/40 experience slow visual decline, with 21% of eyes requiring surgery after 4 years. Clinical and anatomic predictors of vision loss may be distinct from factors associated with earlier surgical intervention.
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http://dx.doi.org/10.1038/s41433-019-0397-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707144PMC
May 2019

Pneumatic Retinopexy Experience and Outcomes of Vitreoretinal Fellows in the United States: A Multicenter Study.

Ophthalmol Retina 2019 02 20;3(2):140-145. Epub 2018 Sep 20.

Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA.

Objective: To evaluate the outcomes of patients undergoing pneumatic retinopexy (PR) performed by vitreoretinal fellows at 6 academic centers in the United States.

Design: Retrospective, multicenter, consecutive case series.

Participants: 483 patients with primary retinal detachments who underwent PR by 49 vitreoretinal fellows from 6 U.S. training sites between 2002 and 2016.

Methods: We reviewed medical records of patients and recorded baseline clinical characteristics (age, sex, baseline visual acuity, lens status, presence of lattice degeneration, presence of vitreous hemorrhage, location of retinal breaks, macular status, and size of detachment), visual and anatomic outcomes at 3-months after PR, as well as training level and PR experience of the fellow at the time of the procedure.

Main Outcome Measures: Single-procedure anatomic success and visual acuity at 3-months follow-up, and association with clinical and training-related factors.

Results: Vitreoretinal fellows performed a variable number of PR, with a median of 7 cases per fellow (range 1-24). Single-procedure anatomic success was 66.8%, and mean LogMAR visual outcome was 0.43 (Snellen equivalent 20/54) at 3 months. Factors that were independently associated with single-procedure success include phakic lens status (P = 0.01), smaller size of retinal detachment (P = 0.02), and the fellow's procedure experience (P = 0.01). The only factor associated with worse visual outcome was baseline visual acuity (P < 0.001).

Conclusion: Vitreoretinal fellows perform variably few pneumatic retinopexies but have outcomes comparable to reported rates by experienced specialists. Procedure experience of individual fellows may impact anatomic outcomes.
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http://dx.doi.org/10.1016/j.oret.2018.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435286PMC
February 2019

Vascular Response to Sildenafil Citrate in Aging and Age-Related Macular Degeneration.

Sci Rep 2019 03 25;9(1):5049. Epub 2019 Mar 25.

Singapore Eye Research Institute, Singapore National Eye Center 11 Third Hospital Avenue, Singapore, 168751, Singapore.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 μm in non-exudative AMD eyes, 196.4 ± 89.8 μm in exudative AMD eyes, and 207.4 ± 77.7 μm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD.
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http://dx.doi.org/10.1038/s41598-019-41509-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434029PMC
March 2019