About

Natalie A. Afshari is a Professor of Ophthalmology at UC San Diego School of Medicine, located at 9500 Gilman Drive, La Jolla, CA. Her research activities and funding focus on the application of RNA-targeting Cas9 to Fuchs' dystrophy and integrative genetic analyses in Fuchs Endothelial Corneal Dystrophy. Her work involves investigating the genetic and molecular mechanisms underlying various ophthalmic conditions, including corneal dystrophies, cataract surgery outcomes, and intraocular lens technologies. She has contributed to numerous publications in the field of ophthalmology, emphasizing advancements in understanding and treating eye diseases through genetic, molecular, and technological approaches.

Research topics

• Medicine
• Immunology
• Pathology
• Biology
• Endocrinology
• Intensive care medicine
• Virology
• Environmental health
• Optometry
• Dermatology
• Internal medicine

Selected publications

• Hematopoietic Stem-Cell Gene Therapy for Cystinosis

  New England Journal of Medicine · 2026-02-18 · 3 citations

  articleOpen access

  BACKGROUND: , the gene encoding cystinosin, a lysosomal transmembrane cystine transporter. In patients with cystinosis, cystine accumulates within lysosomes in all organs. The cystine-depleting agent cysteamine delays but does not prevent disease progression. METHODS: complementary DNA, in patients with cystinosis. The primary end points were the safety and the side-effect profiles of CTNS-RD-04. Secondary end points were measures of efficacy, including white-cell cystine levels and cystine storage depletion. Oral cysteamine was withdrawn before CTNS-RD-04 infusion, and cysteamine eyedrops were withdrawn 1 month after myeloablation. RESULTS: CD34+ cells per kilogram of body weight, and vector copy numbers ranged from 0.59 to 2.91 copies per diploid genome. All the patients had sustained and highly polyclonal hematopoietic reconstitution; vector copy numbers at 24 months ranged from 0.51 to 2.67 copies per diploid genome. A total of 217 adverse events occurred, most of which were mild or moderate in severity and largely consistent with the procedures and underlying disease. No evidence of monoclonal expansion was noted. White-cell cystine levels decreased from baseline except in Patient 4, who had the lowest vector copy number. CONCLUSIONS: In this small study, CTNS-RD-04, an ex vivo gene therapy for cystinosis, had adverse effects that were largely consistent with the myeloablative regimen and underlying disease profile. White-cell cystine levels decreased after therapy. (Funded by the California Institute for Regenerative Medicine and others; ClinicalTrials.gov number, NCT03897361.).

  PublisherOA PDFDOI

• Comprehensive Ocular Characteristics in Cystinosis after Hematopoietic Stem-Cell Gene Therapy Over 24 Months

  American Journal of Ophthalmology · 2026-02-09

  article1st authorCorresponding
  PublisherDOI

• A Cross-Species Hydroquinone Model Replicates Smoking-Related Corneal Endothelial Oxidative Injury and Enables Therapeutic Screening of FGF10

  Investigative Ophthalmology & Visual Science · 2026-03-06

  articleOpen accessSenior authorCorresponding

  Purpose: To establish an in vitro model of smoking-associated oxidative injury to the corneal endothelium and evaluate an injury-mitigating factor. Methods: Primary human and porcine corneal endothelial cells (CEnCs) were exposed to hydroquinone (HQ; 0-150 µM, 48 hours). Outcomes included viability (ATP-based assay), reactive oxygen species (ROS), and apoptosis (TUNEL). Bulk RNA sequencing (RNA-seq) profiled HQ (Nrf2 and Hippo-Yap pathways) and HQ ± fibroblast growth factor 10 (FGF10) responses under moderate stress (cadherin/Wnt programs). FGF10 dose-response (1-100 ng/mL) identified 30 ng/mL for subsequent HQ ± FGF10 studies. Western blotting provided protein validation. Results: HQ caused dose-dependent loss of viability with increased ROS and apoptosis (EC50: 191.2 µM human; 151.2 µM porcine). RNA-seq showed induction of Nrf2 antioxidant/detoxification genes with attenuation of Hippo-Yap signaling. At 150 µM HQ, total Yap decreased and the pYap/Yap ratio increased, consistent with Yap inactivation. FGF10 improved viability across doses (1-100 ng/mL; plateau 30-100 ng/mL) and required cotreatment during HQ exposure. Using 30 ng/mL, FGF10 improved viability across HQ doses, reduced ROS at 100 to 150 µM, and decreased apoptosis at 50 to 100 µM. At 50 µM HQ, FGF10 increased cadherin/Wnt-related transcripts, while N-cadherin protein decreased and β-catenin remained stable, consistent with junctional remodeling rather than full endothelial-mesenchymal transition. Key injury and rescue phenotypes were consistent across species. Conclusions: Our study supports HQ as a translatable in vitro model of smoking-related oxidative stress in CEnCs. FGF10 shows injury-mitigating and pro-regenerative effects, supporting further preclinical evaluation to preserve endothelial integrity and potentially lessen reliance on transplantation in corneal endothelial dystrophies.

  PublisherOA PDFDOI

• Cost-Effectiveness Analysis of Extended Depth of Focus Compared to Trifocal Intraocular Lens in Cataract Surgery

  American Journal of Ophthalmology · 2026-03-05 · 1 citations

  articleSenior author
  PublisherDOI

• Diplopia Following Refractive Lens Exchange

  2025-01-01

  book-chapterSenior author
  PublisherDOI

• Adjuvant Use of Topical 0.05% Cyclosporine A in Primary Pterygium Recurrence Rate: A Systematic Review and Meta-analysis

  American Journal of Ophthalmology · 2025-06-23 · 2 citations

  reviewSenior author
  PublisherDOI

• The evolving fate of the corneal endothelium in cataract surgery

  Current Opinion in Ophthalmology · 2025-11-18

  articleSenior authorCorresponding

  PURPOSE: Cataract surgery, the most commonly performed ophthalmic procedure, can result in corneal endothelial cell loss (ECL), which can have a lasting impact due to the endothelium's limited regenerative capacity. This review highlights surgical technologies and considerations that can provide protection of the corneal endothelium. RECENT FINDINGS: Endothelial cell density (ECD) at birth is about 3,000-5,000 cells/mm 2 and decreases 0.3-0.6% per year, with the adult eye endothelial cell density being approximately 2000-3000 cells/mm 2 . Most ECL occurs within the first three months after surgery, with attributing factors including shallow anterior chamber depth (ACD), low baseline ECD, and high cumulative dissipated energy (CDE), as well as patient-specific comorbidities. Diabetes has been shown to play a role in corneal endothelium recovery, as central corneal thickness (CCT) was found to be significantly higher in diabetic patients after cataract surgery at one month compared to nondiabetic patients, although not at six months in a meta-analysis. Modern fluidics platforms enhance chamber stability and minimize turbulence, and low-perfusion phacoemulsification has decreased ECL rates in high-risk eyes. Corneal tunnel length has been identified as an intraoperative factor; in eyes with short anterior chamber depth, longer tunnel lengths are associated with greater ECL. Microincision surgery, ultrasound energy modulation, and femtosecond laser use provide additional benefits. Hydrogen-enriched irrigating solutions were found to potentially significantly reduce early ECL, and chondroitin sulfate-hyaluronic acid ophthalmic viscosurgical devices (OVDs) further lowered both cell loss and corneal edema. SUMMARY: Advances in surgical technology, combined with individualized planning based on risk factors and anterior segment anatomy, enable minimization of ECL and optimize visual outcomes.

  PublisherDOI

• Investigating the Relationship Between Corneal Dystrophy and Mental Health Conditions Using the All of Us Research Program Database

  American Journal of Ophthalmology · 2025-08-05

  articleSenior author
  PublisherDOI

• Utilization of an automated machine learning approach for the detection of granular corneal dystrophy via slit lamp photographs

  BMC Ophthalmology · 2025-11-22

  articleOpen access

  INTRODUCTION: This study aims to apply automated machine learning (AutoML) techniques for the diagnosis of granular corneal dystrophy (GCD), a rare inherited condition characterized by progressive protein deposition in the corneal stroma. METHODS: Patients diagnosed with GCD who had slit-lamp photographs of the affected eye(s) were enrolled in the study. Individuals with concomitant corneal conditions, ungradable imaging data, or uncertain diagnoses were excluded from the study. Slit-lamp photos depicting the GCD and non-GCD were obtained from the Byers Eye Institute, Stanford University. Image processing included resizing and cropping, focusing solely on the cornea. A deep learning model was subsequently deployed, utilizing Vertex-AI, the AutoML platform developed by Google (Menlo Park, CA). The area under the precision‒recall curve (AUPRC) was plotted, and the sensitivity, specificity, positive predictive value (PPV), accuracy (AC), and F1 score were calculated. RESULTS: The model was trained on a dataset comprising 223 images, consisting of 72 GCD and 151 non-GCD images. One hundred seventy six images were used for training, 24 were used for validation, and 23 were used for testing the model. The AUPRC for the model was 0.995 and precision and recall were both 95.70% at a confidence threshold of 0.5. The sensitivity, specificity, PPV, AC, and F1 score of the model were 93.30%, 100%, 100%, 95.70%, and 0.965, respectively. CONCLUSIONS: A clinician-derived AutoML model successfully identified GCD from slit lamp photographs with high accuracy.

  PublisherDOI

• Investigating Mask-Associated Dry Eye and Contributing Factors in Healthcare Providers

  Clinical ophthalmology · 2025-04-01 · 4 citations

  articleOpen accessSenior author

  Purpose: To evaluate mask-associated dry eye among healthcare providers and assess the impact of glasses, contact lenses, and mask types on ocular surface parameters. Patients and Methods: This prospective study included 50 healthcare providers who wore face masks throughout the day and 10 control subjects who did not. Ocular surface assessments were conducted in the morning and after a full workday. Assessments included the Ocular Surface Disease Index (OSDI), tear osmolarity, tear breakup time (TBUT), ocular staining score, Schirmer I test, and LipiView™ interferometer parameters: lipid layer thickness (LLT), Meibomian gland dropout (MGd), incomplete/complete blinks, and partial blinking rate (PBR). Results: Fifty healthcare providers (mean age 39.83 ± 12.3 years) and 10 controls (mean age 29.40 ± 14.43 years) were included. Mask use averaged 7.15 ± 1.15 hours daily. Mask use was associated with a significant increase in OSDI scores compared to controls (mean change 4.50 ± 10.17 vs − 1.00 ± 1.94; P = 0.041) and a larger decrease in TBUT in the right eye (mean change − 1.65 ± 3.37 vs 0.30 ± 1.57; P = 0.008) and left eye (mean change − 1.40 ± 2.91 vs − 1.20 ± 1.93; P = 0.046). No significant changes were observed in tear osmolarity, LLT, MGd, or Schirmer I results. Glasses were correlated with a smaller decrease in TBUT in the right eye (r 2 = 0.085, P = 0.044) and left eye (r 2 = 0.125, P = 0.013). Conclusion: Mask use is associated with increased OSDI scores and decreased TBUT, potentially worsening dry eye disease. Glasses may offer some protection, but further research is needed to fully address mask-associated dry eye. Keywords: dry eye, tear break-up time, tear film

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Recent grants

• Integrative Genetic Analyses in Fuchs Endothelial Corneal Dystrophy

  NIH · $1.2M · 2013–2017

Frequent coauthors

• Ruti Sella

  Tel Aviv University

  75 shared

• Yi‐Ju Li

  60 shared

• Ron A. Adelman

  55 shared

• Robert N. Weinreb

  University of California, San Diego

  49 shared

• Gordon K. Klintworth

  Duke University

  41 shared

• Simon G. Gregory

  41 shared

• Hideki Fukuoka

  Kyoto Prefectural University of Medicine

  34 shared

• Mollie Minear

  National Institutes of Health

  34 shared