Keratoconus - An Inflammatory Disease in Disguise
For decades, textbooks defined keratoconus as a 'non-inflammatory' degenerative thinning of the cornea. But a growing body of peer-reviewed research is challenging that assumption, revealing elevated inflammatory cytokines, oxidative stress, mitochondrial dysfunction, and altered protease activity in the tears and corneal tissue of affected patients. In this episode, host Maya Iyer sits down with Dr. Saikumar Gandapodi, Board-Certified Doctor of Oriental Medicine, Ayurvedic practitioner, and Founder and Director of Netra Eye Institute, to explore why keratoconus may be far more of an inflammatory and systemic disease than its classic definition suggests.
Together they trace the mechanistic story — from matrix metalloproteinases and IL-6 and TNF-alpha in tear film, to reactive oxygen species, glutathione depletion, and the biomechanical collapse of collagen crosslinks. Dr. Gandapodi explains where conventional pillars like corneal crosslinking, rigid contact lenses, and transplantation excel, and where adjunct opportunities may exist to address the underlying biological terrain, including the gut-eye axis, eye rubbing, atopy, and oxidative burden.
The conversation introduces Netra Restoration Therapy (NRT) as an integrative, complementary framework — never a replacement for standard care — and interprets traditional herbal medicine through the modern lenses of network pharmacology and systems biology. Balanced, evidence-aware, and intellectually honest, this episode is for clinicians, patients, and curious minds who want to understand keratoconus not as an isolated corneal shape problem, but as a whole-person biological process.
Transcript
Welcome to the Netra Eye Institute Podcast,
Speaker:where modern vision science meets the wisdom of integrative ophthalmology.
Speaker:Today, we are joined by Dr. Saikumar Gandepudi,
Speaker:founder and director of Netra Eye Institute,
Speaker:whose work is dedicated to redefining how patients understand and approach chronic
Speaker:and degenerative eye conditions. His goal is simple: to help patients, families, and
Speaker:clinicians explore a more comprehensive and integrative approach to long-term eye
Speaker:health.
Speaker:This is the Netra Eye Institute Podcast. Let's begin.
Speaker:Welcome to The Integrative Eye, the podcast where cutting-edge ophthalmology
Speaker:meets systems biology.
Speaker:I'm your host, Maya Iyer.
Speaker:Today, we're exploring a condition that most textbooks have quietly mislabeled for
Speaker:decades, keratoconus.
Speaker:Long called a non-inflammatory disease, it may be anything but.
Speaker:To guide us, I'm joined by Dr. Sai Kumar Gandepudi, board-certified doctor of
Speaker:Oriental medicine, a practitioner of Ayurvedic medicine, and founder and
Speaker:director of Netra Eye Institute, a holistic eye care center.
Speaker:Dr. Gandepudi, welcome.
Speaker:Thank you, Maya. It’s a pleasure.
Speaker:Keratoconus is one of my favorite topics, precisely because it forces us to rethink
Speaker:an old label.
Speaker:The moment we stop seeing it as just a misshapen cornea and start seeing it as a
Speaker:biological process, the whole conversation changes.
Speaker:Before we dive in, many listeners will have heard you mention Netra Restoration
Speaker:Therapy.
Speaker:In one breath, what is it?
Speaker:In short, Netra Restoration Therapy, or NRT, is a full-spectrum, multi-target
Speaker:integrative platform.
Speaker:Rather than chasing one mechanism, it aims to support several at once.
Speaker:Ocular blood flow, neurotrophins like BDNF and NGF,
Speaker:mitochondrial function,
Speaker:oxidative stress reduction,
Speaker:inflammatory balance, and the whole body factors that feed into eye health.
Speaker:It’s an adjunct to conventional care, never a replacement and never a cure.
Speaker:Chronic eye disease is multifactorial, so the approach has to be a system, not a
Speaker:single pill.
Speaker:Let’s start with the classic teaching.
Speaker:Why has keratoconus been called non-inflammatory for so long?
Speaker:Historically, clinicians looked for the visible signs of inflammation,
Speaker:redness, white blood cell infiltration, pain, and keratoconus doesn’t show those,
Speaker:so it was grouped with the degenerative dystrophies.
Speaker:But absence of visible inflammation is not absence of molecular inflammation.
Speaker:Once we could measure cytokines and enzymes in the tear film,
Speaker:-that old definition started to crack. -So what did the molecular evidence
Speaker:actually show? Why does this happen at the tissue level?
Speaker:Several groups found that tears from keratoconus patients carry elevated
Speaker:inflammatory markers.
Speaker:Lima and Duran, publishing in Ophthalmology back in two thousand and
Speaker:five, reported increased IL-6 and TNF alpha and higher matrix
Speaker:metalloproteinase nine activity in these patients.
Speaker:MMP-9 is a collagen-degrading enzyme,
Speaker:so you have a pro-inflammatory environment quietly digesting the very collagen
Speaker:scaffolding that keeps the cornea dome-shaped.
Speaker:That’s why the cornea thins and bulges into a cone.
Speaker:That reframes the cone as a symptom, not the disease itself.
Speaker:What are researchers learning about oxidative stress in this picture?
Speaker:This is a crucial thread. Work led by researchers like M. Christina Kenney and
Speaker:colleagues showed that keratoconic corneas have impaired antioxidant defenses,
Speaker:reduced ability to clear reactive oxygen species, altered levels of enzymes like
Speaker:aldehyde dehydrogenase and superoxide dismutase, and accumulation of oxidative
Speaker:and nitrative damage markers.
Speaker:The cornea is one of the most oxygen-exposed and UV-exposed tissues in
Speaker:the body, so when antioxidant capacity fails, damage accumulates.
Speaker:Mitochondrial DNA damage has also been reported,
Speaker:so oxidative stress and inflammation are really feeding each other in a loop.
Speaker:You mentioned mitochondria.
Speaker:How central is mitochondrial dysfunction here?
Speaker:It’s emerging but compelling.
Speaker:Studies have found increased mitochondrial DNA mutations and evidence of oxidative
Speaker:damage to mitochondrial components in keratoconic tissue. When mitochondria
Speaker:underperform, cells produce more reactive oxygen species and have less energy to
Speaker:repair the extracellular matrix.
Speaker:For the keratocytes, the cells maintaining corneal collagen, that’s a double blow.
Speaker:More damage, less repair capacity.
Speaker:I’d characterize this as promising mechanistic evidence, mostly from
Speaker:laboratory and tissue studies, not yet a settled clinical target.
Speaker:Let’s talk about behavior and systemic links.
Speaker:Eye rubbing comes up constantly.
Speaker:Where does that fit?
Speaker:Eye rubbing may be the bridge between inflammation and mechanics.
Speaker:Vigorous rubbing raises corneal temperature, triggers release of
Speaker:inflammatory mediators, and applies repeated mechanical stress that can spike
Speaker:matrix metalloproteinase activity.
Speaker:Many keratoconus patients also have atopy,
Speaker:allergic eye disease, eczema, asthma.
Speaker:Which is itself an inflammatory itch-driven state.
Speaker:So the itch leads to rubbing, the rubbing amplifies inflammation and protease
Speaker:activity,
Speaker:and the collagen weakens.
Speaker:It’s a vicious cycle, and it’s one of the most modifiable factors we have.
Speaker:You’ve written about the gut eye axis.
Speaker:How could the gut possibly influence a corneal disease?
Speaker:Here I want to be careful and honest.
Speaker:This is emerging and largely hypothesis-generating for keratoconus
Speaker:specifically. But the logic is grounded. A compromised intestinal barrier, sometimes
Speaker:called leaky gut, can allow bacterial components like lipopolysaccharide into
Speaker:circulation,
Speaker:raising systemic inflammatory tone,
Speaker:the same TNF alpha and IL-6 pathways we see elevated in keratoconus tears.
Speaker:The gut microbiome also shapes systemic oxidative balance and immune regulation.
Speaker:So the concept is that a patient’s overall inflammatory terrain, partly set in the
Speaker:gut, may influence how aggressively a cornea deteriorates.
Speaker:I present that as a plausible systems-level hypothesis,
Speaker:-not proven causation. -That’s a helpful distinction.
Speaker:Now,
Speaker:what does conventional ophthalmology do exceptionally well here,
Speaker:and where are its limits?
Speaker:Conventional care is excellent and often essential.
Speaker:Corneal cross-linking, pioneered by Theo Seiler and Gregor Wollensak, whose
Speaker:foundational work appeared around two thousand and three
Speaker:in the American Journal of Ophthalmology,
Speaker:uses riboflavin and UVA light to create new collagen bonds and halt progression.
Speaker:That’s a genuine breakthrough.
Speaker:Rigid gas-permeable lenses restore vision, and corneal transplantation rescues
Speaker:advanced cases.
Speaker:Where these approaches are limited is that they primarily address structure and
Speaker:mechanics.
Speaker:Cross-linking stiffens collagen, but it doesn’t directly quiet the underlying
Speaker:inflammatory and oxidative environment that helped weaken the tissue.
Speaker:That’s the gap where adjunct strategies may add value.
Speaker:So the surgery fixes the wall but not necessarily the weather. Let’s explore the
Speaker:adjunct side.
Speaker:How do you think about herbal medicine scientifically rather than as folklore?
Speaker:I think of them as complex, multicomponent, multitarget pharmacology.
Speaker:A single herb may contain dozens of bioactive compounds,
Speaker:and a classical formula can contain hundreds or thousands of phytochemicals
Speaker:acting on many pathways at once.
Speaker:Modern researchers now study this using network pharmacology, transcriptomics, and
Speaker:metabolomics.
Speaker:So instead of one molecule hitting one receptor,
Speaker:you may have a system nudging inflammation down, supporting endothelial and
Speaker:antioxidant function, and protecting mitochondria simultaneously. For a
Speaker:multifactorial disease, that systems-level profile is conceptually appealing,
Speaker:though I always stress the clinical evidence in ophthalmology is still early.
Speaker:Can you give a concrete example of a compound and its biological rationale?
Speaker:Take curcumin from turmeric, deeply relevant in Ayurveda.
Speaker:In laboratory and animal studies, it modulates NF-kappa B signaling, lowering
Speaker:TNF alpha, IL-6, and IL-1 beta,
Speaker:and it scavenges reactive oxygen species.
Speaker:Given that those exact cytokines are elevated in keratoconus tears, the
Speaker:mechanistic overlap is striking.
Speaker:Green tea catechins and quercetin have similar antioxidant and MMP-modulating
Speaker:signals in vitro.
Speaker:But I want to be clear,
Speaker:these are mostly bench and animal data, not large human corneal trials.
Speaker:The rationale is strong. The clinical proof is a work in progress.
Speaker:Several traditional systems describe keratoconus in their own language.
Speaker:Can you translate a couple of those concepts into biomedical terms?
Speaker:Gladly, as conceptual parallels, not exact equivalents.
Speaker:In traditional Chinese medicine, what’s called blood stasis may loosely correspond
Speaker:to impaired microcirculation and poor tissue perfusion,
Speaker:while liver blood deficiency, which governs the eyes, might parallel
Speaker:inadequate nourishment and repair of ocular tissue.
Speaker:In Ayurveda, an aggravated pitta with disturbed rakta dhatu maps reasonably onto
Speaker:a heated, inflammatory, oxidative state,
Speaker:which fits the inflammatory picture we’ve discussed.
Speaker:These are interpretive frameworks that guided treatment for centuries.
Speaker:Modern science lets us test which physiological correlates actually hold up.
Speaker:Where does neurotrophin biology enter?
Speaker:We hear a lot about BDNF and NGF in retinal disease.
Speaker:-Do they matter for the cornea? -The cornea is one of the most densely
Speaker:innervated tissues in the body, and those nerves release neurotrophic factors like
Speaker:NGF that support epithelial health and wound healing.
Speaker:Nerve growth factor eye drops, Cenegermin, are already approved for neurotrophic
Speaker:keratitis, which shows the cornea genuinely responds to neurotrophin
Speaker:support.
Speaker:In keratoconus, corneal nerve architecture is altered, and there’s interest in
Speaker:whether supporting NGF and reducing inflammation could improve tissue
Speaker:resilience.
Speaker:It’s an active, exciting research frontier rather than established therapy.
Speaker:How does Netra Restoration Therapy pull all of this together for a real patient?
Speaker:NRT works alongside the ophthalmologist.
Speaker:If a patient needs cross-linking or lenses, they get that first. That’s
Speaker:non-negotiable.
Speaker:Around it, we address the terrain: reducing eye rubbing and treating atopy,
Speaker:lowering oxidative and inflammatory burden through targeted nutrition and
Speaker:antioxidants,
Speaker:supporting mitochondrial and vascular function, and looking upstream at gut and
Speaker:systemic inflammation.
Speaker:The philosophy is simple:
Speaker:stabilize the structure conventionally and improve the biological environment
Speaker:integratively.
Speaker:No guarantees, no cure claims, just a rational, evidence-aware attempt to give
Speaker:the tissue a better chance.
Speaker:What emerging research excites you most right now?
Speaker:Two things.
Speaker:First, tear film biomarker profiling.
Speaker:Using proteomics to catch the inflammatory and oxidative signature early, before the
Speaker:cornea visibly deforms.
Speaker:That could shift us from reactive to preventive.
Speaker:Second, the systemic and microbiome angle.
Speaker:Properly designed studies asking whether calming whole-body inflammation slows
Speaker:progression.
Speaker:If keratoconus really is an inflammatory disease in disguise, then the future of
Speaker:care won’t only be on the cornea—it’ll be in the whole person.
Speaker:That’s a powerful place to land.
Speaker:Any final thought for patients listening?
Speaker:Yes. Please don’t rub your eyes.
Speaker:Follow your ophthalmologist’s guidance closely. And know that your cornea is
Speaker:connected to the rest of your biology.
Speaker:Structure and terrain matter together.
Speaker:There’s real reason for hope when we treat both.
Speaker:Dr. Sekumar Gandapoti,
Speaker:thank you for a genuinely illuminating conversation.
Speaker:To our listeners, thank you for joining The Integrative Eye
