Rising Star: Introducing Viha Vig, MBChB

The desire to do research was primal for Viha Vig, MBChB, who watched her father, a chemical engineer, develop water- and fire-proof material from the time she was a teenager in India. “My journey in research started because I wanted to do something similar. I wanted to find things that can be helpful and make them available to communities,” Vig said. She is in the Murray-to-Mountains Rural Generalist Intern Training Program, Victoria, Australia, and completed her MBChB at the University of Auckland, New Zealand, in 2025.

She was confident in her decision to continue on the research path and, in so doing, studied biochemistry and molecular biology to earn her BA from Boston University, Boston. However, this was the time point at which her path diverged slightly, and she inadvertently got hooked into her first ophthalmology randomized controlled trial.¹ The trial looked promising to her because of the potential for results to be translated into clinical care. In light of this, she switched to a medical track under the mentorship of Manju Subramanian, MD, associate professor at Boston University and vice chair of faculty affairs in the Department of Ophthalmology, who specializes in vitreoretinal disease and surgery.

New perspective

Following that switch to the medical side, she realized the importance of personal communication with patients on a daily basis and how valuable translational research can be when it is used to treat patients. “A benefit for me was the joy I experienced when patients benefit from that research and its translation into the clinic. That is the goal and what propels me,” she said.

Subramanian was and remains a strong influence in Vig’s progress. “Despite moving among 4 countries, India, the US, New Zealand, and Australia, she maintained her faith in me, my ideas, and hypotheses and never rejected them but encouraged research and discussion. Her encouragement gave me the confidence to believe that my ideas could be helpful in ophthalmology and other areas,” Vig commented.

Reaping rewards from research

The vision overlying Vig’s research is comprised of identifying both useful treatments that can result in improved quality of care and identifying the multidisciplinary connections between the eye and other organs. The research has been impactful in the following areas.

Oral vs. intravenous (IV) sedation in ocular surgery

Her participation in a randomized clinical trial at Boston Medical Center resulted in publication in the Journal of Vitreoretinal Disease.¹ The study, which was part of the Boston Medical Center Oral vs IV (OIV) Sedation clinical trial program, included 84 participants and addressed the primary outcome of patient satisfaction with oral and IV sedation during vitreoretinal surgery; the secondary outcomes were surgeon and anesthesia satisfaction, need for supplemental anesthesia, and surgical complications.

The results demonstrated the noninferiority of oral sedation (P = 0.002) to IV sedation. No significant differences were found in surgeon or anesthesia satisfaction or major intraoperative complications. Five patients receiving oral (11.9%) and three receiving IV (7.1%) sedation required supplemental intravenous sedation (difference, 4.8%; P = 0.46),¹ the authors reported.

Kaiser Permanente Colorado² conducted a large retrospective study of over 21,000 office-based cataract surgeries with similar results, demonstrating that the model was safe and effective—and leading to cataract surgeries being routinely performed in minor procedure rooms without an anesthesiologist on site. The potential for this anesthesia approach to impact access to care and quality of life is significant for resource-limited settings globally, including India, Vig explained.

A secondary analysis of the OIV clinical trial dataset investigated which patient, surgeon, and anesthesia provider characteristics predicted higher satisfaction with oral sedation specifically.³

“Shorter length of surgery was positively associated with higher patient and surgeon satisfaction with oral sedation. Other factors, including non-White race and non-English primary language, were associated with higher patient satisfaction. Additional IV sedation needed during surgery was associated with worse patient, surgeon, and anesthesia provider satisfaction. Tailoring oral sedation to procedures that are shorter in duration may help maximize the success of oral sedation as an alternative to intravenous sedation,”³ according to Dr. Vig.

Postmortem cortical tissue analysis linking vitreous humor biomarkers to chronic Alzheimer’s disease and traumatic encephalopathy (CTE)⁴

This was one of the first such studies to link vitreous humor biomarkers specifically to CTE and among the first to detect Aβ42/40 and pTau181 in the vitreous samples of patients with Alzheimer’s disease. The retrospective postmortem study included 41 eyes of patients with Alzheimer’s disease, CTE, both diseases, and control groups.

The results showed that the postmortem vitreous humor biomarker levels were significantly correlated with Alzheimer’s disease and CTE pathology in corresponding brains, while vitreous neurofilament light chain was correlated with the CTE staging. This exploratory study indicated that biomarkers in the vitreous humor may serve as a proxy for neuropathologic disease, Vig and colleagues concluded. She added, “Using the retina as a means of non-invasive diagnosis could ameliorate access and affordability, especially in remote regional and rural areas globally.”

Platelet-derived growth factor, age-related macular degeneration (AMD), and COVID-19 genome-wide pleiotropy study⁵

In this study, Vig and colleagues established an association between a gene in patients with AMD and the risk of COVID-19 outcomes, she explained.

Specifically, they identified novel genome-wide significant associations near the plate-derived growth factor subunit B (PDGFB) gene (best single-nucleotide polymorphism: rs130651) in the pleiotropy analysis of the two diseases. “The disease-risk allele of rs130651 was significantly associated with increased gene expression levels of PDGFB in multiple tissues and immune cells. PDGFB expression was higher in AMD cases than AMD controls and in the peak COVID-19 symptom stage compared to the early/progressive stage among COVID-19 patients over age 40 and age 50. The analysis found that the liability of AMD risk derived from complement system dysfunction, hospitalization, infection, and increased levels of serum cytokine PDGF-BB were significantly associated with COVID-19 outcomes.”

UK Biobank Studies

Mitochondrial disease and dementia

Vig originated the hypothesis that mitochondrial disease, both ocular and systemic, may independently confer risk for dementia.^6,7 Brainstorming with her team extended this central question into 3 related hypotheses, each forming the basis of a separate study: the association between ocular and systemic mitochondrial disease and dementia; the association between retinal vascular occlusions (RVO and RAO) and dementia; and the association between herpetic eye disease and dementia. Together, these studies form a programmatic body of work using the eye as a window into neurodegeneration.

Specifically, they identified novel genome-wide significant associations near the plate-derived growth factor subunit B (PDGFB) gene (best single-nucleotide polymorphism: rs130651) in the pleiotropy analysis of the 2 diseases. “The disease-risk allele of rs130651 was significantly associated with increased gene expression levels of PDGFB in multiple tissues and immune cells. PDGFB expression was higher in AMD cases than AMD controls and in the peak COVID-19 symptom stage compared to the early/progressive stage among COVID-19 patients over age 40 and age 50. The analysis found that the liability of AMD risk derived from complement system dysfunction, hospitalization, infection, increased levels of serum cytokine PDGF-BB were significantly associated with COVID-19 outcomes.

Vig is currently engaged in research into ocular and systemic mitochondrial diseases and dementia.^7,8,

In this retrospective trial, which was one of the first in humans on this subject, she and her colleagues investigated the relationship between mitochondrial disorders, particularly those with ocular involvement, and the prevalence, incidence, and risk of dementia; a full manuscript is currently under review.

The key study findings⁶ presented at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology were

• The prevalence of dementia was significantly higher in all mitochondrial subgroups than in controls: 18.7% (ocular), 15.0% (systemic), and 17.4% (combined) vs. 2.7% in controls.
• The adjusted odds ratios for risk were notably elevated: 5.39 for ocular, 2.88 for systemic, and 6.84 for the combined group. The ocular group had a sharper increase in dementia risk despite no systemic involvement.
• The age-adjusted incidence of all-cause dementia per 1,000 person-years was 22.3 in the ocular group, 17.1 in the systemic group, and 26.8 in the combined group, compared with 3.4 in the control population.
• Cox regression analysis showed that the ocular group had a 3.86-fold increased hazard ratio for developing dementia after adjusting for key covariates such as hypertension, diabetes, and smoking history.

Retinal vascular occlusions and dementia

This large retrospective longitudinal cohort study⁸ that included over 500,000 UK Biobank participants investigated if retinal vascular occlusions, retinal vein occlusion (RVO), and retinal artery occlusion are independently associated with all-cause dementia, Alzheimer's disease, and vascular dementia.

The study concluded that retinal vascular occlusions and RVO are not independent risk factors of all-cause dementia but may serve as clinical indicators prompting cognitive investigation, as individuals with RVO have a higher risk of vascular dementia. Adjustment for shared risk factors found no association between dementia and retinal vascular occlusions. Findings from this study are both consistent and in conflict with prior reports and indicate that the connection between retinal vascular occlusions and neurodegenerative diseases causing dementia may be due to their shared pathogenesis and risk factors,⁸ according to the investigators.

Herpetic eye disease and dementia

The third study, currently in progress, investigates whether herpetic eye disease, encompassing herpes simplex and herpes zoster ophthalmicus, is associated with an increased risk of dementia (manuscript in preparation). The mechanistic rationale draws on growing evidence that neurotropic herpesviruses can establish latency within ocular and neural tissues and may contribute to neuroinflammatory pathways implicated in Alzheimer’s disease pathogenesis.

A takeaway for ophthalmologists and optometrists: insights into AI and the importance of retrospective studies

Contrary to the common belief that randomized clinical trials are the gold standard for conducting research, Dr. Vig emphasized the growing importance of retrospective studies for surgical specialties in her mind—an area of research where investigators often face several barriers to conducting RCTs ethically, which prolongs the duration of execution and obtaining meaningful clinically translatable results.

Based on her research experience, she realized that many databases often are not connected with epidemiology and genetics. “Perhaps the individuals building data sets should think about including known genetic associations or known biomarkers and some biochemistry and epidemiology because of the need for more robust evidence,” she stated.

Considering the growing use of AI and the increasing growth of data sets, gathering more data that includes more diverse information would be more beneficial to future generations of scientists than culling data that are easily gathered, she opined.

In line with this absence of critical data, she cited a Nature Medicine perspective⁹ that described how AI “is accelerating faster than the educational frameworks designed to govern it” and the attendant risk that medical trainees who “rely on AI during the early formative years of clinical education may fail to develop the foundational reasoning skills that safe, independent practice requires.”

The authors called this “never-skilling,” as opposed to “deskilling in experienced clinicians and from mis-skilling, in which uncritical acceptance of AI errors leads trainees to internalize flawed clinical knowledge as fact.”

The authors proposed the following steps: “establishing AI-independent baseline competency, building critical calibration through structured pedagogy, and integrating AI under supervision in medical training.”

“For me, the most exciting place AI belongs right now, and one that sidesteps the risk of never-skilling⁹ almost entirely, is in building large, structured, comprehensive databases from complex clinical data. This is especially valuable in surgical research, where randomized controlled trials are often logistically and ethically difficult. AI-assisted data curation at scale can generate the kind of retrospective evidence base that would take years to build manually, without ever substituting for the clinician's judgment.” For Vig, the goal is deliberate engagement.

She continued, “Use AI as your co-pilot, not your autopilot. A co-pilot is engaged, informed, and ready to take the controls. An autopilot is something you delegate to and stop paying attention.”

Viha Vig, MBChB

E: [email protected]

Vig is in the Murray-to-Mountains Rural Generalist Intern Training Program, Victoria, Australia. She has no proprietary interest in any aspect of this report.

References

1. Siegel NH, Fiorello MG, Ness S, et al. Oral vs IV Sedation (OVIS) Study Group. Patient satisfaction with oral vs intravenous sedation for vitrectomy surgery: a randomized, noninferiority clinical trial. J Vitreoretin Dis. 2021;6:201–9. doi: 10.1177/24741264211027820.

2. Ianchulev T, Litoff D, Ellinger D, Stiverson K, Packer M. Office-based cataract surgery: population health outcomes study of more than 21,000 cases in the United States. Ophthalmology. 2016;123:723–8. doi: 10.1016/j.ophtha.2015.10.041.

3. 3.Sampani K, Hussain Am Sanjiv N, et al. Factors associated with satisfaction with oral sedation during ophthalmic surgeries. Oral versus Intravenous Sedation Study Group. Graefe's Arch Clin Exp Ophthalmol. 2025;263:1565-72. doi: 10.1007/s00417-025-06781-1.

4. 4.Vig V, Garg I, Tuz-Zahra F, et al.Vitreous humor biomarkers reflect pathological changes in the brain for Alzheimer's disease and chronic traumatic encephalopathy. J Alzheimers Dis. 2023;93:1181–93. doi: 10.3233/JAD-230167.

5. 5.Chung J, Vig V, Sun X, et al. Genome-wide pleiotropy study identifies association of PDGFB with age-related macular degeneration andCOVID-19 infection outcomes. J Clin Med.2022;12:109. doi: 10.3390/jcm12010109.

6. Vig V, et al. Association between ocular and systemic mitochondrial diseases and dementia: a retrospective cross-sectional study using the UK Biobank. Invest Ophthalmol Vis Sci. 2025;66 (ARVO Annual Meeting Abstract). https://iovs.arvojournals.org/article.aspx?articleid=2804672&resultClick=1

7. Vig V. Eyeing the brain: How ocular mitochondrial disease may predict dementia risk. Ophthalmology Times Europe. 2026;21:30-1. https://europe.ophthalmologytimes.com/view/eyeing-the-brain-how-ocular-mitochondrial-disease-may-predict-dementia-risk

8. 8.Gao A, Tuz-Zahar F, Vig V, et al. The association between retinal vascular occlusions and dementia: A UK Biobank retrospective longitudinal study. Ophthalmol Retina. 2026;10:128–34. doi: 10.1016/j.oret.2025.08.010.

9. Ke Y, Jin L, Ong JCL, et al. AI-induced never-skilling in medical education. Nat Med. 2026. https://doi.org/10.1038/s41591-026-04438-y