LVPEI Monthly Note: Clinician-Scientist Model | April 2026

News from our full member LV Prasad Eye Institute

Some time ago, Anthony Aldave, a celebrated ophthalmologist and the director of the Corneal Genetics Laboratory at the Jules Stein Eye Institute in California, visited us at LVPEI. Muralidhara Ramappa, head of LVPEI’s Centre for Rare Eye Diseases, and Tony share an interest in rare, congenital corneal disorders. In the course of their conversations, Murali made an observation: among children with Congenital Hereditary Endothelial Dystrophy (CHED), more boys seemed to be turning up in his clinic than girls. CHED is a rare condition; only 3 out of 100,000 newborns in European populations develop this condition. While the prevalence is higher in south Asia, its rarity still makes it hard to identify a pattern from clinical observation alone.

Tony and his colleagues at the University of California Los Angeles (UCLA) took Murali’s insight forward to test this observation in their lab. What followed exemplifies the spirit of enquiry that defines our work; clinical intuition/observation, leading to laboratory investigation and findings brought back to inform patient care.

Rare diseases

CHED is one of many rare, hereditary conditions that are found at a higher frequency in our region, partly due to consanguinity, the cultural practice of marrying close relatives in a family (or, in genetic terms, marriage between two people who share a common ancestor). The practice is prevalent in the Middle East, South and South East Asia. In India, consanguineous marriages account for an estimated 10% of all unions and are associated with a higher risk of genetic disorders including rare ocular genetic
disorders like CHED. CHED is caused by mutations in a single gene, SLC4A11, which leads to increased oxidative stress, corneal cell dysfunction, and eventual cell death. The disease follows an autosomal recessive pattern–a child must inherit two copies of the mutated gene, one from each parent, to develop the condition.

Tony is a leader in genetic corneal dystrophies, and his work has done much to help our understanding of many of these conditions, including CHED. Murali and his colleagues have managed nearly 900 families affected by this condition, making us one of the largest referral centres for this rare condition. Such scale creates a fertile ground for serendipitous insights that might otherwise remain unnoticed. That day, Tony and Murali discussed CHED’s odd pattern in LVPEI patient histories: most patients with the condition were boys.

The Role of Sex as a biological variable

What began as a clinical observation led to a collaborative research effort between LVPEI, the Stein Eye Institute, and AIIMS, New Delhi. The findings were striking. CHED in boys presents with a more severe pattern of the disease and they need surgery at a relatively younger age. They exhibit a higher level of oxidative stress and corneal swelling. Their work resulted in the first set of definitive evidence that sex is a key biological variable to determine CHED severity. The research also identified that oestrogen, a female sex hormone that is predominant in girls and women, has a protective role to play. In experimental models, the removal of ovaries (which produce oestrogen) in female mice led to a rapid worsening of
CHED, suggesting that hormonal differences significantly modulate disease expression. This has important implications: while CHED is a ‘Mendelian disorder’ (caused by a mutation to a single gene) and an attractive candidate for gene therapy, future clinical trials must account for sex differences to ensure accurate and effective outcomes.

The Clinician-Scientist Model

LVPEI’s founding nearly 40 years ago drew inspiration from leading American institutions where our founder trained and collaborated with over the years. Central to that vision was the clinician–scientist model.

At LVPEI too today, the clinician–scientist model represents a deliberate integration of patient care with scientific inquiry, wherein clinical observations inform research questions and research findings, in turn, refine clinical practice. This philosophy is operationalized through a structured framework that allocates protected time for research and fosters close collaboration between clinicians and basic scientists. Such an approach ensures that research is not abstract or isolated, but directly rooted in real-world clinical challenges. By enabling a continuous “bench-to-bedside and bedside-to-bench” cycle, LVPEI has created an ecosystem where innovation is both contextually relevant and ultimately translatable, eading to tangible improvements in diagnosis, treatment, and delivery of eye care.

The CHED story is one among many such stories here.

For years, a mysterious infection, later identified as Pythium keratitis, was often mistaken for fungal disease. Patients treated with antifungals saw little to no response and leading to severe vision loss and even loss of the infected eye. Work led by Savitri Sharma & Bhupesh Bagga along with other colleagues at LVPEI helped characterise this organism (which looks like a fungus under a microscope, but is closer to algae than fungi). They also discovered that the infection responds to antibiotics, not antifungals. Today, this work has significantly improved outcomes and established Pythium keratitis as a distinct clinical entity in ophthalmology.

In another example, translational research led by Virender Sangwan and Geeta Vemuganti and later, Sayan Basu, transformed the management of ocular surface diseases. The development of Simple Limbal Epithelial Transplantation (SLET) procedure revolutionized the management of patients with severe ocular surface damage due to chemical burns, like the accidental squirting of choona (lime) into a person’s eye.

Before this innovation, the management of such cases was dependent on complex, resource-intensive, lab-based stem cell expansion techniques. SLET eliminated the need for specialized laboratory infrastructure and made stem cell– based ocular surface reconstruction accessible, affordable, and scalable. Today, SLET has been adopted worldwide as a standard of care for patients with severe ocular
surface damage.

Sustaining a culture of inquiry

Institutions endure because their founding vision is sustained by practice patterns that reinforce the original vision. At LVPEI, the clinician-scientist model has enabled a continuous exchange between the clinic and laboratory, allowing us to generate insights that are both scientifically rigorous and relevant to the patient. This approach benefits not only our patients, but also our collaborators and their patients across the world, so that all may see.

-Prashant Garg

Date: 29 April 2026
Source: LV Prasad Eye Institute