Publications by authors named "Peter Y Zhao"

11 Publications

  • Page 1 of 1

Association of No-Cost Genetic Testing Program Implementation and Patient Characteristics With Access to Genetic Testing for Inherited Retinal Degenerations.

JAMA Ophthalmol 2021 Mar 4. Epub 2021 Mar 4.

W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor.

Importance: The benefits of no-cost genetic testing initiatives have not been characterized. The no-cost My Retina Tracker Genetic Testing Study (MRT-GTS) research registry for inherited retinal degenerations (IRDs) was launched in 2017 in the US.

Objective: To investigate the associations of MRT-GTS implementation and patient characteristics with access to genetic testing for IRDs.

Design, Setting, And Participants: In a cross-sectional design, analysis of new patients evaluated 12 months before (July 1, 2016, to June 13, 2017) and 12 months after (June 14, 2017, to June 30, 2018) MRT-GTS implementation at a single academic referral eye center was conducted. Participants included 369 patients with IRD. Data analysis was conducted from February to June 2020.

Main Outcomes And Measures: Change in rates of successfully obtaining genetic testing, odds ratios (ORs) of association between patient characteristics and obtaining testing, and days elapsed from clinic visit to reporting of results.

Results: Among 369 patients (mean [SD] age, 39.5 [20.8] years; 193 [52.3%] women), 144 were evaluated in the pre-MRT-GTS period and 225 in the post-MRT-GTS period. The baseline rate of successfully obtaining testing was 51.4% (95% CI, 42.6%-60.2%). The initiation of MRT-GTS was associated with a 28.9-percentage point increase in testing rate (95% CI, 16.7%-41.1%; P < .001). Patient characteristics that increased the odds of obtaining testing were eligibility for MRT-GTS (OR, 14.15; 95% CI, 7.36-27.24; P < .001) and worse visual acuity (logMAR +1.0; Snellen equivalent decrease from 20/20 to 20/200) in the better-seeing eye (OR, 1.92; 95% CI, 1.27-2.91; P < .01). Patients had decreased odds when identifying as Black or African American (OR, 0.10; 95% CI, 0.04-0.24; P < .001) or other race (OR, 0.37; 95% CI, 0.15-0.91; P = .03) compared with White race, and when the primary language was not English (OR, 0.13; 95% CI, 0.03-0.55; P < .01). The proportion of test results reported within 90 days was 81.5% (95% CI, 74.8%-86.4%) when eligible for MRT-GTS compared with 48.1% (95% CI, 35.6%-58.1%) when not eligible (P < .001).

Conclusions And Relevance: In this study, the implementation of MRT-GTS was associated with an increase in the proportion of patients who successfully obtained testing, suggesting the potential clinical value of this approach. Patient-level demographic and clinical factors appear to be associated with decisions to pursue testing.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934082PMC
March 2021

Cystoid macular edema precipitated by altitude in a patient with X-linked retinitis pigmentosa.

Ophthalmic Genet 2020 06 13;41(3):275-278. Epub 2020 May 13.

Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan , Ann Arbor, Michigan, USA.

Background: X-linked retinitis pigmentosa (XLRP) is a hereditary retinopathy that may present with cystoid macular edema (CME). The exact cause of CME in XLRP is unknown. We describe a case report of new-onset CME precipitated by travel to high altitude in an adult with XLRP, but no known prior history of CME.

Case Description: A 38-year-old man with XLRP caused by a hemizygous pathogenic variant in (c.372del; p.Glu125fs) reported sudden onset bilateral blurry vision 4 days after ascending to an altitude of 3,700 m. He sought local ophthalmic care and was found to have severe bilateral CME. He was treated with topical and oral carbonic anhydrase inhibition and instructed to return to normal altitude. Follow-up imaging at normal altitude revealed that the CME was nearly completely resolved 4 days after initial presentation, and completely resolved 2 weeks after initial presentation.

Conclusion: Vascular and metabolic changes caused by retinal degeneration in XLRP may predispose to the development of CME under the hypoxic conditions experienced at high altitudes. We advise that retinal specialists treating patients with RP should caution them on traveling to high altitudes that could precipitate or exacerbate CME.
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http://dx.doi.org/10.1080/13816810.2020.1762901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941113PMC
June 2020

SEROLOGY NEGATIVE BARTONELLA NEURORETINITIS IN AN IMMUNOCOMPROMISED PATIENT.

Retin Cases Brief Rep 2020 Mar 3. Epub 2020 Mar 3.

Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan.

Background/purpose: To report a case of serology-negative severe disseminated Bartonella neuroretinitis in an immunocompromised patient in which diagnosis was made by detection of B. henselae DNA by universal polymerase chain reaction of brain tissue.

Methods: Case report.

Results: A 57-year-old man with immunoglobulin A vasculitis on immunosuppressive therapy presented with lethargy, weight loss, and bilateral decreased vision. Fundus examination revealed bilateral mild vitritis, marked optic disc edema, vascular sheathing, and numerous white inner retinal and preretinal lesions. Brain magnetic resonance imaging revealed multiple foci of restricted diffusion and a ring-enhancing focus in the left parietal lobe. Serologies, cerebrospinal fluid, and vitreous biopsies were all negative for Bartonella. A brain biopsy was performed and B. henselae DNA was detected by universal polymerase chain reaction of the specimen. The patient demonstrated resolution of fundus findings with antibiotic treatment. Repeat serological testing demonstrated seroconversion.

Conclusion: In immunocompromised patients, infection by Bartonella henselae can present as severe disseminated disease. Establishing the diagnosis can be challenging as serologic testing is often unrevealing in the setting of a blunted immune response. Polymerase chain reaction has been used in select cases to establish the diagnosis.
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http://dx.doi.org/10.1097/ICB.0000000000000995DOI Listing
March 2020

Blurred Vision and Wrinkled Retinas in an Elderly Man.

JAMA Ophthalmol 2019 02;137(2):226-227

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.6254DOI Listing
February 2019

A Flushed Face and Dilated Retinal Veins.

JAMA Ophthalmol 2018 12;136(12):1414-1415

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.3300DOI Listing
December 2018

A Worldwide Price Comparison of Glaucoma Medications, Laser Trabeculoplasty, and Trabeculectomy Surgery.

JAMA Ophthalmol 2018 11;136(11):1271-1279

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor.

Importance: Medical and surgical interventions for glaucoma are effective only if they are affordable to patients. Little is known about how affordable glaucoma interventions are in developing and developed countries.

Objective: To compare the prices of topical glaucoma medications, laser trabeculoplasty, and trabeculectomy relative with median annual household income (MA-HHI) for countries worldwide.

Design, Setting And Participants: Cross-sectional observational study. For each country, we obtained prices for glaucoma medications, laser trabeculoplasty, and trabeculectomy using government pricing data, drug databases, physician fee schedules, academic publications, and communications with local ophthalmologists. Prices were adjusted for purchasing power parity and inflation to 2016 US dollars, and annual therapy prices were examined relative to the MA-HHI. Interventions costing less than 2.5% of the MA-HHI were considered affordable.

Main Outcomes And Measures: Daily cost for topical glaucoma medications, cost of annual therapy with glaucoma medications, laser trabeculoplasty, and trabeculectomy relative to MA-HHI in each country.

Results: Data were obtained from 38 countries, including 17 developed countries and 21 developing countries, as classified by the World Economic Outlook. We observed considerable variability in intervention prices compared with MA-HHI across the countries and across interventions, ranging from 0.1% to 5% of MA-HHI for timolol, 0.1% to 27% for latanoprost, 0.2% to 17% for laser trabeculoplasty, and 0.3% to 42% for trabeculectomy. Timolol was the most affordable medication in all countries studied and was 2.5% or more of MA-HHI in only 2 countries (5%). The annual cost of latanoprost was 2.5% or more of MA-HHI in 15 countries (41%) (15 developing countries [75%] and no developed countries). The cost of laser trabeculoplasty was 2.5% or more of the MA-HHI in 15 countries (44%) (11 developing countries [65%] and 4 developed countries [24%]). The cost of trabeculectomy was 2.5% or more of the MA-HHI in 28 countries (78%) (18 developing countries [95%] and 10 developed countries [59%]). In 18 countries (53%), laser trabeculoplasty cost less than a 3-year latanoprost supply.

Conclusions And Relevance: For many patients worldwide, the costs of medical, laser, and incisional surgical interventions were 2.5% or more of the MA-HHI. Successfully reducing global blindness from glaucoma requires addressing multiple contributing factors, including making glaucoma interventions more affordable.
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http://dx.doi.org/10.1001/jamaophthalmol.2018.3672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248183PMC
November 2018

Peripheral Pigmented Retinal Lesions in Stargardt Disease.

Am J Ophthalmol 2018 04 27;188:104-110. Epub 2017 Dec 27.

W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan. Electronic address:

Purpose: To investigate the prevalence of peripheral pigmented retinal lesions and associated clinical findings in patients with Stargardt disease.

Design: Retrospective case series.

Methods: Records at a single academic institution were reviewed for patients with genetically confirmed Stargardt disease with peripheral pigmented retinal lesions on wide-field retinal imaging. For this cohort we described demographics, clinical features, and pathogenic variants.

Results: Out of 62 patients with Stargardt disease and wide-field retinal imaging, 14 had peripheral pigmented retinal lesions. These flat, subretinal lesions were located in the mid or far periphery and had well-defined borders, resembling congenital hypertrophy of retinal pigment epithelium (CHRPE) lesions. For this group of 14 patients, median age at initial diagnosis of Stargardt disease was 9.5 years, and the median duration of disease was 21.5 years. Median Snellen visual acuity was 20/200, and median central scotoma size was 20.0 degrees. All 14 patients had electroretinographic abnormalities. Four out of 14 patients developed new lesions during clinical follow-up.

Conclusions: Wide-field retinal imaging revealed the presence of peripheral pigmented retinal lesions resembling CHRPE lesions in a subset of patients with genetically confirmed Stargardt disease. Presence of these lesions may be associated with severe phenotypes of the disease.
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http://dx.doi.org/10.1016/j.ajo.2017.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994923PMC
April 2018

Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression.

Exp Eye Res 2016 10 1;151:179-89. Epub 2016 Sep 1.

Dept. of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA; Dept. of Ophthalmology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:

Mutations of claudin-19 cause severe ocular deficits that are not easily reconciled with its role in regulating the outer blood retinal barrier. ARPE-19 is a widely used culture model of the retinal pigment epithelium (RPE). ARPE-19 is unique among epithelial cell lines, because it expresses all tight junction proteins except claudin family members. ARPE-19 also loses aspects of the RPE phenotype with cell passage. This study asks whether exogenous expression of the main RPE claudins, claudin-3 and claudin-19, would restore RPE phenotype, and whether these claudins have distinct roles in RPE. An Ussing chamber was used to measure the transepithelial electrical resistance and transepithelial electrical potential. These measurements were used to estimate the permeability co-efficients of ions. The transepithelial diffusion of polyethylene glycols were used to examine the leak pathway of tight junctions. Wound-healing, quantitative RT-PCR and immunoblotting examined diverse aspects of the RPE phenotype. Over-expression of either claudin decreased the permeability of small ions and polyethylene glycol. Both claudins were slightly cation-specific, but claudin-3 was less permeable to large solutes. Claudin expression widely affected gene expression to partially restore RPE phenotype. Claudins redistributed filamentous actin from stress fibers to circumferential bands associated with tight junctions, and made wound-healing more epithelial-like. Both claudins increased the expression of genes related to RPE core functions and increased steady-state levels of phosphorylated-AKT. In conclusion, claudin-3 and claudin-19 formed general permeability barriers and affected cell morphology, proliferation, migration, AKT signaling, and gene expression. When claudins are exogenously expressed, ARPE-19 more closely model native RPE.
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http://dx.doi.org/10.1016/j.exer.2016.08.021DOI Listing
October 2016

Comparison of Outcomes of Laser Trabeculoplasty Performed by Optometrists vs Ophthalmologists in Oklahoma.

JAMA Ophthalmol 2016 Oct;134(10):1095-1101

Dean McGee Eye Institute, Department of Ophthalmology, University of Oklahoma College of Medicine, Oklahoma City.

Importance: Oklahoma is one of the few states where optometrists have surgical privileges to perform laser trabeculoplasty (LTP). Optometrists in other states are lobbying to obtain privileges to perform LTP and other laser procedures. Little is known whether outcomes of patients undergoing this procedure by optometrists are similar to those undergoing LTP by ophthalmologists.

Objective: To compare outcomes of LTPs performed by ophthalmologists with those performed by optometrists to determine whether differences exist in the need for additional LTPs.

Design, Setting, And Participants: This retrospective longitudinal cohort study used a health care claims database containing more than 1000 eyes of Medicare enrollees with glaucoma who underwent LTP in Oklahoma from January 1, 2008, through December 31, 2013. For each procedure, the data specify the type of eye care professional who performed the LTP. The rate of LTPs performed by ophthalmologists that required 1 or more additional LTPs in the same eye was compared with the rate of LTPs performed by optometrists. Regression models determined factors affecting risk of undergoing more than 1 LTP in the same eye.

Main Outcomes And Measures: Proportion of enrollees requiring additional LTPs, hazard ratio with 95% CIs of undergoing additional LTPs.

Results: A total of 1384 eyes of 891 eligible patients underwent LTP from January 1, 2008, through December 31, 2013. There were 1150 eyes that received LTP (83.1%) by an ophthalmologist and 234 eyes (16.9%) that had the procedure performed by an optometrist. The mean (SD) age at the initial LTP was 77.7 (7.5) years for enrollees with ophthalmologist-performed LTP and 77.6 (8.0) years for those with optometrist-performed LTP (P = .89). Among the 1384 eyes receiving LTP, 258 (18.6%) underwent more than 1 LTP in the same eye. The proportion of eyes undergoing LTP by an optometrist requiring 1 or more subsequent LTP session (35.9%) was more than double the proportion of eyes that received this procedure by an ophthalmologist (15.1%). Medicare beneficiaries undergoing LTP by optometrists had a 189% increased hazard of requiring additional LTPs in the same eye compared with those receiving LTP by ophthalmologists (hazard ratio, 2.89; 95% CI, 2.00-4.17; P < .001) after adjusting for potential confounders.

Conclusions And Relevance: Considerable differences exist among the proportions of patients requiring additional LTPs comparing those who were initially treated by ophthalmologists with those initially treated by optometrists. Health policy makers should be cautious about approving laser privileges for optometrists practicing in other states until the reasons for these differences are better understood.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.2495DOI Listing
October 2016

TRP Channels Localize to Subdomains of the Apical Plasma Membrane in Human Fetal Retinal Pigment Epithelium.

Invest Ophthalmol Vis Sci 2015 Mar 3;56(3):1916-23. Epub 2015 Mar 3.

Department of Surgery, Yale University, New Haven, Connecticut, United States Department of Ophthalmology & Visual Science, Yale University, New Haven, Connecticut, United States.

Purpose: Calcium regulates many functions of the RPE. Its concentration in the subretinal space and RPE cytoplasm is closely regulated. Transient receptor potential (TRP) channels are a superfamily of ion channels that are moderately calcium-selective. This study investigates the subcellular localization and potential functions of TRP channels in a first-passage culture model of human fetal RPE (hfRPE).

Methods: The RPE isolated from 15- to 16-week gestation fetuses were maintained in serum-free media. Cultures were treated with barium chloride (BaCl2) in the absence and presence of TRP channel inhibitors and monitored by the transepithelial electrical resistance (TER). The expression of TRP channels was determined using quantitative RT-PCR, immunoblotting, and immunofluorescence confocal microscopy.

Results: Barium chloride substantially decreased TER and disrupted cell-cell contacts when added to the apical surface of RPE, but not when added to the basolateral surface. The effect could be partially blocked by the general TRP inhibitor, lanthanum chloride (LaCl3, ~75%), or an inhibitor of calpain (~25%). Family member-specific inhibitors, ML204 (TRPC4) and HC-067047 (TRPV4), had no effect on basal channel activity. Expression of TRPC4, TRPM1, TRPM3, TRPM7, and TRPV4 was detected by RT-PCR and immunoblotting. The TRPM3 localized to the base of the primary cilium, and TRPC4 and TRPM3 localized to apical tight junctions. The TRPV4 localized to apical microvilli in a small subset of cells.

Conclusions: The TRP channels localized to subdomains of the apical membrane, and BaCl2 was only able to dissociate tight junctions when presented to the apical membrane. The data suggest a potential role for TRP channels as sensors of [Ca(2+)] in the subretinal space.
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http://dx.doi.org/10.1167/iovs.14-15738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364639PMC
March 2015

Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells.

J Invest Dermatol 2015 May 18;135(5):1405-1414. Epub 2014 Sep 18.

Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address:

Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation.
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http://dx.doi.org/10.1038/jid.2014.411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364923PMC
May 2015