DefEYE data show corneal healing in early neurotrophic keratitis

A peer-reviewed study evaluating serial application of decellularized basement membrane (DBM) (Biovance Ocular; DefEYE) in patients with subclinical or Mackie Stage 1 neurotrophic keratitis (NK) found corneal epithelial resolution in all eyes with complete follow-up, according to a company announcement from DefEYE, Inc.¹ The retrospective analysis, authored by Brandon D. Ayres, MD, and colleagues, included nearly 1,000 patients and appeared in Clinical Ophthalmology.²

“[NK] is likely more prevalent than we believe. Should we conduct the appropriate corneal sensitivity testing at patient presentation of symptoms, I believe we will uncover more patients for whom we can intervene sooner, particularly with interventional approaches such as decellularized basement membrane,” Ayres said in the company’s statement.¹

Study overview

The retrospective study, titled “Retrospective evaluation of successive Biovance decellularized basement membrane tissue grafts for the management of chronic subclinical and Stage 1 neurotrophic keratitis,” evaluated outcomes of serial DBM graft placement stratified by Brill severity grade.² According to the company’s summary of the findings, corneal epithelial resolution occurred in all eyes with complete follow-up.¹ Functional corneal sensitivity improved in 0.7% of Brill 3 eyes, 31.6% of Brill 4 eyes, and 77.5% of Brill 5 eyes, and mean graft utilization increased with disease severity, ranging from 3.08 grafts in Brill 4 eyes to 4.30 grafts in Brill 5 eyes.¹ Among eyes with abnormal baseline tear film osmolarity, 70% to 82% normalized following treatment, and matrix metalloproteinase-9 (MMP-9) positivity decreased across all severity groups, with 56% to 66% converting to negative.¹

Clinical context

NK is a degenerative corneal disease caused by impaired trigeminal nerve innervation, resulting in reduced corneal sensitivity and impaired epithelial healing; estimates of its prevalence vary widely, from roughly 5 to 11 per 10,000 individuals, reflecting both its rarity and its likely underrecognition in clinical practice.³ Current management is staged by Mackie classification, progressing from preservative-free lubrication and amniotic membrane therapy in mild disease to recombinant human nerve growth factor (cenegermin) or autologous serum tears for more advanced or persistent cases.⁴ Corneal sensitivity testing, a key diagnostic step, is not routinely performed in general ophthalmic practice, which may contribute to underdiagnosis, particularly in early-stage disease that can resemble dry eye disease.⁴

Mechanism and prior evidence

DBM grafts are placental-derived tissue products intended to support epithelial healing by providing a scaffold and biologic factors similar to those used in amniotic membrane therapy, an already-established treatment modality in ocular surface disease.⁴ The company positions serial DBM application as a potential earlier intervention for subclinical or Stage 1 NK, a disease stage for which current management is largely limited to supportive care.¹

Interpretive framing

The finding of universal epithelial resolution in eyes with complete follow-up is notable, though the varying degree of sensitivity improvement across severity grades—minimal in Brill 3 eyes despite epithelial healing—suggests epithelial closure and functional nerve recovery may not track together, a distinction relevant to how clinicians counsel patients on expected outcomes.¹

Open questions and next steps

This was a retrospective, uncontrolled case series without a comparator arm, so the independent contribution of DBM grafts relative to natural disease course or concurrent supportive therapies cannot be determined from this design alone.² The proportion of patients lost to follow-up, and how “complete follow-up” was defined, were not detailed in the company’s summary.¹ Ayres is scheduled to present related real-world cohort data at the American Academy of Ophthalmology annual meeting in New Orleans, Louisiana, October 10–12, 2026.¹

Q&A: Ayres on recognizing and intervening in early NK

Ophthalmology Times (OT) reached out to Ayres for his perspective on the underdiagnosis of NK, the study’s key findings, and how the data might translate into clinical practice.

Note: Transcript lightly edited for clarity and length.

OT: What’s driving the underdiagnosis of NK, and what should a general ophthalmologist do differently at the slit lamp to catch it earlier?

Ayres: Early NK frequently masquerades as dry eye disease. This underdiagnosis occurs in large part because eye care professionals do not routinely test corneal sensitivity, and because early NK may present with nonspecific ocular surface findings that overlap with classic dry eye disease. Importantly, the relative absence of symptoms should not be reassuring because reduced corneal innervation can create a disconnect between the severity of clinical signs and the patient’s reported discomfort.

Eye care professionals should have a lower threshold for assessing corneal sensitivity whenever the degree of staining appears disproportionate to symptoms (stain without pain), the ocular surface fails to respond as expected to conventional dry-eye therapy, or the patient has recognized risk factors for corneal nerve dysfunction such as history of refractive surgery, systemic diabetes, and chronic glaucoma therapy.

OT: Corneal epithelial resolution occurred in all eyes with complete follow-up, but sensitivity improvement varied widely by Brill severity grade. What’s the explanation for that gap between epithelial healing and measurable sensitivity recovery?

Ayres: Epithelial resolution and recovery of corneal sensitivity represent related but biologically distinct processes. In this study, serial DBM was associated with epithelial resolution across eyes with complete follow-up, whereas improvement in corneal sensitivity varied according to baseline Brill severity. Interestingly, eyes with more severe baseline disease demonstrated a disproportionately greater measurable improvement in sensitivity. One explanation is that these eyes had greater baseline impairment and therefore greater capacity for detectable improvement; whereas eyes with milder disease had less room to improve on the Brill scale. In addition, restoration of epithelial integrity may occur more rapidly than recovery of corneal nerve function, so resolution of staining does not necessarily translate into an immediate or equivalent change in measured sensitivity. These findings suggest that epithelial resolution and sensory improvement should be viewed as complementary, but distinct, measures of response to serial DBM.

OT: This is a retrospective, uncontrolled series in nearly 1,000 patients. What would a prospective study need to confirm before this becomes standard practice?

Ayres: A prospective study would need to confirm that the improvements seen retrospectively are reproducible under a predefined protocol and are attributable to serial DBM rather than natural history, concurrent therapy, or selection bias. Ideally, this would include a controlled comparison, standardized entry criteria and staging, masked assessment where feasible, and objective endpoints such as corneal staining, corneal sensitivity, MMP-9, and osmolarity.

Most importantly, it should establish which patients benefit most, how many applications are typically required, how durable the response is, and whether earlier intervention reduces progression to more advanced neurotrophic disease. Confirmation of safety, reproducibility across multiple centers, and clinically meaningful differences versus current standard management would provide the strongest basis for broader adoption as standard practice.

OT: Decellularized basement membrane is described as a potential first-line approach so long as corneal sensitivity has been compromised and documented. Practically speaking, what’s the threshold or test that should trigger that intervention?

Ayres: The trigger should not necessarily be a specific numerical cutoff. Practically, it is the combination of epithelial compromise and documented reduction in corneal sensitivity. If a patient has persistent or recurrent punctate epithelial staining and corneal sensitivity is clearly reduced, especially in the setting of risk factors, that should raise concern for early neurotrophic disease rather than simply refractory dry eye. Sensitivity can be assessed qualitatively at the slit lamp with a cotton wisp or dental floss, or quantitatively with a Brill or Cochet-Bonnet esthesiometer.

The goal is to intervene while the disease is still at the epitheliopathy stage, rather than waiting for a persistent epithelial defect. The newer NKSG classification specifically recognizes altered sensation before keratopathy as stage 1 and epitheliopathy with punctate epithelial keratopathy as stage 2, reinforcing the concept that neurotrophic disease begins well before an epithelial defect develops. In that context, documented hypoesthesia together with persistent epithelial staining provides a clinically meaningful threshold for considering an epithelial-supportive intervention, such as DBM.

Brandon D. Ayres, MD

E: [email protected]

Ayres specializes in cornea and external disease, anterior segment, and refractive surgery with Ophthalmic Partners of Pennsylvania on Bala-Cynwyd, Pennsylvania, and is co-director, Cornea Fellowship Program at Wills Eye Hospital in Philadelphia.

References

1. DefEYE announces publication of peer-reviewed article highlighting use of decellularized basement membrane in almost 1000 patients with neurotrophic keratitis. DefEYE, Inc. News release. August 18, 2026. Accessed August 18, 2026.

2. Ayres BD, Fram NR, Wu HK, Feulner L, Desai NR. Retrospective evaluation of successive Biovance eecellularized basement membrane tissue grafts for the management of chronic subclinical and Stage 1 neurotrophic keratitis. Clin Ophthalmol. 2026;20:599498. doi:10.2147/OPTH.S599498

3. Neurotrophic keratitis. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; updated 2025. Accessed August 18, 2026. https://www.ncbi.nlm.nih.gov/books/NBK431106/

4. Roshan M, et al. Neurotrophic keratitis: diagnosis, management, and future directions. CRSToday. January 14, 2025. Accessed August 18, 2026. https://crstoday.com/articles/jan-2025/neurotrophic-keratitis-diagnosis-management-and-future-directions