About

Paul S. Bernstein, MD, PhD, is a principal investigator at the Bernstein Laboratory within the Department of Ophthalmology at the University of Utah School of Medicine. His research focuses on the biochemistry and biophysics of nutritional interventions aimed at combating inherited and acquired ocular disorders. Dr. Bernstein's National Eye Institute-funded laboratory is a leader in studying the proteins involved in the uptake and stabilization of lutein and zeaxanthin, dietary xanthophyll carotenoids that protect the human macula from light-induced oxidative damage. Elevated ocular levels of these carotenoids are associated with a decreased risk of age-related macular degeneration. In collaboration with Dr. Werner Gellermann, he developed patented resonance Raman spectroscopy instrumentation to non-invasively measure carotenoid levels in the eye, skin, and other tissues, technology that has been widely adopted by the nutritional supplementation industry worldwide. Dr. Bernstein's research also extends to genetic studies of macular dystrophies and degenerations, supported by the Foundation Fighting Blindness. He has contributed to defining the roles of the ABCR and ELOVL4 genes in macular disease and demonstrated that high dietary intake of omega-3 fatty acids can protect against dominant Stargardt macular dystrophy (STGD3) in a large Utah family with an ELOVL4 mutation. He has authored over fifty peer-reviewed articles and reviews, six book chapters, and serves as a reviewer for numerous journals and foundations. Additionally, he is among the first researchers to test the early diagnostic capabilities of fluorescence lifetime imaging ophthalmoscopy (FLIO), a novel non-invasive retinal imaging technique. Dr. Bernstein's work has helped establish the importance of lutein, zeaxanthin, and omega-3 fatty acids in maintaining macular health. He served as the Moran Eye Center principal investigator for the National Eye Institute's AREDS II study, a nationwide clinical trial that established nutritional recommendations for age-related macular degeneration. His investigations into the molecular mechanisms of proteins associated with inherited macular degeneration offer hope for future molecular interventions.

Research topics

• Medicine
• Internal medicine
• Surgery
• Ophthalmology
• Pediatrics
• Biochemistry
• Chemistry
• Biology

Selected publications

• Carotenoid Status and Psychological Impact of Presymptomatic Macular Degeneration Genetic Risk Assessment: The MAGENTA Randomized Trial

  Ophthalmology Science · 2026-01-23

  articleOpen accessSenior author

  Purpose: Genetic testing for age-related macular degeneration (AMD) risk reliably offers insight into an individual's susceptibility for future visual loss; however, an American Academy of Ophthalmology expert panel in 2012 discouraged routine AMD genetic risk testing because there was no evidence that such knowledge would alter an individual's clinical course. To address this knowledge gap, we investigated whether disclosure of AMD genetic risk to presymptomatic individuals would encourage healthier lifestyle adoption that could reduce the incidence of AMD later in life. Design: The Moran AMD Genetic Testing Assessment (MAGENTA) trial is a single-site, prospective, controlled clinical study (NCT05265624) that randomized 80 presymptomatic subjects in a 3:1 ratio to immediate or 1-year deferred disclosure groups. We stratified participants into high-, intermediate-, and low-risk groups by Mendelian randomization. Subjects: We enrolled Whites aged 18 to 64 years with no clinical signs of AMD. Methods: As a biomarker of healthy nutritional status, participants' skin, plasma, and macular carotenoid concentrations were measured using resonance Raman and reflectance spectroscopies, high-performance liquid chromatography, and autofluorescence imaging, respectively. Nutritional and emotional status were assessed with validated surveys. Main Outcome Measures: We looked for changes in skin, plasma, and macular carotenoids as biomarkers of healthier lifestyle adoption and for the impact of AMD genetic risk disclosure on participants' psychological well-being. Results: > 0.05 for all comparisons). Participants' interest and compliance were high, as shown by the 95% subject study completion rate, and there was no evidence of worsening stress following AMD genetic risk disclosure to the participants. Conclusions: While AMD genetic risk disclosure did not significantly impact nutritional biomarker levels over 12 months, there were no adverse psychological effects, and the subjects generally felt knowledge of their AMD risk was valuable. Our findings could guide future presymptomatic AMD genetic testing trials with extended biomarker assessments in larger and more diverse populations. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  PublisherOA PDFDOI

• Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice

  Life · 2025-12-23

  articleOpen accessSenior author

  Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile-elevating HDL cholesterol and lowering TG-which may contribute to protection against AMD and other lipid-associated diseases.

  PublisherOA PDFDOI

• Head-mounted surgical robots are an enabling technology for subretinal injections

  Science Robotics · 2025-02-19 · 8 citations

  articleOpen access

  Therapeutic protocols involving subretinal injection, which hold the promise of saving or restoring sight, are challenging for surgeons because they are at the limits of human motor and perceptual abilities. Excessive or insufficient indentation of the injection cannula into the retina or motion of the cannula with respect to the retina can result in retinal trauma or incorrect placement of the therapeutic product. Robotic assistance can potentially enable the surgeon to more precisely position the injection cannula and maintain its position for a prolonged period of time. However, head motion is common among patients undergoing eye surgery, complicating subretinal injections, yet it is often not considered in the evaluation of robotic assistance. No prior study has both included head motion during an evaluation of robotic assistance and demonstrated a significant improvement in the ability to perform subretinal injections compared with the manual approach. In a hybrid ex vivo and in situ study in which an enucleated eye was mounted on a human volunteer, we demonstrate that head-mounting a high-precision teleoperated surgical robot to passively reduce undesirable relative motion between the robot and the eye results in a bleb-formation success rate on moving eyes that is significantly higher than the manual success rates reported in the literature even on stationary enucleated eyes.

  PublisherOA PDFDOI

• Assessment of Skin Carotenoids among School Children

  Journal of Nepal Health Research Council · 2025-02-14

  articleOpen accessSenior author

  BACKGROUND: This study aimed to assess skin carotenoid measurement among children in the Hill region of Nepal. METHODS: School children between 3 to 7 years old from six schools were enrolled in the study. Skin carotenoid levels were assessed using the Veggie Meter® (Longevity Link Corporation, Salt Lake City, Utah, USA). Detailed eye evaluations were conducted in subjects with low skin carotenoid scores (<150 Reflectance Units(RU)) and/or those with a history of night blindness. RESULTS: A total of 324 school children were enrolled in the study with mean age of 5.12±1.33 years. The mean skin carotenoid score was 163±71 RU, ranging from 1 to 363 RU. The skin carotenoid level was <150 RU in 46.9% of children and between 150 and 200 RU in 23.5% of children. Low skin carotenoid scores (<150 RU) were found in 17% of 3 year olds, 28.3% each of 4 and 5 year olds, 20.4% of 6 year olds, and 11.2% of 7 year olds. In multivariate analysis, age was significantly associated with low skin carotenoid scores (p=0.003; OR; 2.02; 95% CI: 1.28- 3.19). Odds of having <150 RU was 2.02 times more among the children up to five years old as compared to those over five years of age. CONCLUSIONS: Nearly half of the school children had low skin carotenoid scores. Skin carotenoid score was significantly lower among the lower age group. These findings emphasize the need to enhance awareness to consume plenty of green leafy vegetables and fruits in the diet.

  PublisherDOI

• Natural History of Microperimetry and Optical Coherence Tomography in USH2A-Retinopathy: A Structure-Function Association Study

  American Journal of Ophthalmology · 2025-05-03 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Delayed-onset Moraxella nonliquefaciens endophthalmitis following intravitreal injection

  American Journal of Ophthalmology Case Reports · 2025-07-02 · 1 citations

  articleOpen accessSenior authorCorresponding

  To report a case of Moraxella nonliquefaciens endophthalmitis presenting one month after intravitreal injection. An 84-year-old man presented to the retina clinic with vision loss, pain, and redness in his right eye 28 days after a routine intravitreal injection of faricimab for exudative age-related macular degeneration. The patient had a remote history of cataract surgery, rhegmatogenous retinal detachment repair, and scleral buckle explant for exposure 3 years prior. The patient was found to have endophthalmitis, characterized by a hypopyon and dense vitritis. Broad-spectrum intravitreal antimicrobials and dexamethasone were administered, and a vitreous tap returned sterile. The patient achieved initial quiescence, but he had two recurrences of inflammation in this eye over the next 4.5 months. The patient ultimately underwent pars plana vitrectomy, vitreous biopsy, intraocular lens explant, capsulectomy and repeat intravitreal antimicrobial injections for definitive treatment. Broad-range PCR testing detected Moraxella nonliquefaciens . Inflammation resolved after surgery without further recurrence in the subsequent 7-month post-operative period. Moraxella species have been implicated in cases of endophthalmitis associated with glaucoma filtering surgery and trauma, but this report details a delayed-onset Moraxella nonliquefaciens- associated endophthalmitis after intravitreal injection. • M. nonliquefaciens can cause a post-injection, delayed-onset endophthalmitis • Vitreous biopsy with broad-range PCR testing can aid detection of rare microbes • Definitive treatment may require vitrectomy, lens explant, and capsulectomy

  PublisherDOI

• Skin Carotenoid Assessment Modalities

  Methods and protocols in food science · 2025-01-01 · 1 citations

  book-chapterSenior author
  PublisherDOI

• Mechanism of Lutein to <i>meso</i> -Zeaxanthin Isomerization by RPE65 Catalysis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-13

  preprintOpen access

  Abstract The macular pigments lutein (L), zeaxanthin (Z), and meso -zeaxanthin (MZ) protect the human retina from light and oxidative stress. While L and Z are abundant in the human diet, MZ is nearly absent. We previously demonstrated MZ is derived from L in chicken embryos precisely timed with expression of RPE65. Herein, we show that RPE65 from mouse, an animal that does not concentrate MZ in the eye, catalyzes L to MZ isomerization similarly as found for RPE65 from chicken and human, when expressed in cultured cells. Co-expression with xanthophyll-binding proteins had no impact on MZ yield. L and MZ both fit deep into the tunnel accessing the non-heme iron center, with strain evident for the 3’R , 6’R ε ring of L. Interestingly, a negatively charged Glu148, found along substrate tunnel, highly conserved among carotenoid cleavage dioxygenases, and which is critical for eye health, could be replaced by a neutral, isosteric residue (Gln) without impacting MZ yield. We propose that L to MZ isomerization proceeds by a neutral, radical transition state that differs from the carbocation encountered during retinoid isomerization. These findings extend our mechanistic understanding for macular carotenoid metabolism and should be considered when developing therapeutic interventions that act via RPE65.

  PublisherDOI

• The Moran AMD Genetic Testing Assessment (MAGENTA) Trial

  Current Developments in Nutrition · 2024-06-29

  articleOpen accessSenior author

  4 C had 97% stability at 3 months which reduced to 93% at 11 months; -20 C had 100% stability at 11 months but degraded by 16 months.RT light dropped below 95% stability at 4.5 weeks after baseline and RT dark dropped below 95% stability at 7 weeks.Syringes delivered an average (95% CI) percent of target mass of 101.4% (99.2, 103.6).Conclusions: Vitamin A displayed higher rates of degradation in heat and light.VA in capsules stored at -20 C was stable for 11 months.Single-use syringes were accurate when used by a single technician and merit a larger sample size to determine usability.

  PublisherOA PDFDOI

• The Progression of Stargardt Disease (ProgStar) as determined by spectral-domain optical coherence tomography over a 24-month period (ProgStar Report No. 19)

  Ophthalmic Research · 2024-07-18 · 4 citations

  articleOpen access

  INTRODUCTION: The aim of this study was to evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed ABCA4-associated Stargardt disease type 1 (STGD1) over a 24-month period in a multicenter prospective cohort study. METHODS: SD-OCT images from 428 eyes of 236 patients were analyzed. Change of mean thickness (MT) and intact area were estimated after semiautomated segmentation for the following individual layers in the central subfield (CS), inner ring (IR), and outer ring (OR) of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OSs), inner segments (IS), outer nuclear layer (ONL) inner retina (IR), and total retina. RESULTS: Statistically significant decreases of all outer retinal layers (RPE, OS, IS, and ONL) could be observed over a 24-month period both in decline of mean retinal thickness and intact area (p &lt; 0.0001, respectively), whereas the IR showed an increase of retinal thickness in the CS and IR and remained unchanged in the OR. CONCLUSIONS: Significant loss could be detected in outer retinal layers by SD-OCT over a 24-month period in patients with STGD1. Loss of thickness and/or intact area of such layers may serve as potential endpoints for clinical trials that aim to slow down the disease progression of STGD1.

  PublisherDOI

Recent grants

• NIH Grant R29EY011600

  NIH · $648k · 2003

• Biochemistry and Pharmacology of the Macular Carotenoids

  NIH · $7.7M · 1997–2027

• University of Utah Core Vision Research Grant

  NIH · $15.0M · 2005–2029

Frequent coauthors

• Aruna Gorusupudi

  University of Utah

  85 shared

• Werner Gellermann

  Longevity Biotech (United States)

  66 shared

• Rupert W. Strauß

  Medical University of Graz

  65 shared

• Lydia Sauer

  University of Utah

  61 shared

• Binxing Li

  55 shared

• Hendrik P. N. Scholl

  University Hospital of Basel

  54 shared

• Prakash Bhosale

  51 shared

• Preejith Vachali

  ARUP Laboratories (United States)

  47 shared

Education

• B.S., Chemistry

  Harvard University

• M.D., Division of Health Sciences and Technology

  Harvard University

• Ph.D., Biochemistry and Pharmacology of Rhodopsin Regeneration in the Vertebrate Eye

  Harvard University

Awards & honors

• 2020 Mildred Weisenfeld Award from the Association for Resea…
• 2019 W. Richard Green Lecture by the Macula Society
• 2016 Outstanding Humanitarian Service Award from the America…