Dry Eye Disease for Neurotrophic Keratopathy

(THINK Trial)

Overseen By Leslie Lemieux

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Research Insight LLC

Disqualifiers: Ocular surgery, Herpes infection, Ocular inflammation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand corneal sensitivity in people with Stage 1 Neurotrophic Keratopathy (NK), a condition related to dry eye disease that can affect vision. Researchers seek ways to identify patients who might need a specific treatment called rhNGF (recombinant human nerve growth factor) in the future to maintain their eyesight. The trial focuses on individuals with dry eye disease, particularly those experiencing persistent eye dryness and discomfort, noticeable corneal staining, and short tear break-up time (when tears evaporate too quickly). Participants should not have had recent eye surgery or any active eye infections. As an unphased trial, this study offers patients the opportunity to contribute to foundational research that could lead to new treatments for dry eye conditions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinator or your doctor.

What prior data suggests that this method is safe for evaluating corneal sensitivity in patients with Stage 1 Neurotrophic Keratopathy?

Research shows that treatments for dry eye disease are generally safe and well-tolerated by patients. Studies have not found any major safety issues. These treatments aim to restore balance to the tear film, the thin layer of tears covering the eye, which helps reduce discomfort and keep eyes healthy.

While side effects can occur with any treatment, serious problems are rare. Mild symptoms like temporary eye irritation might occur but are usually easy to manage. Dry eye treatments have been used for a long time and are considered safe.

This trial examines how the treatment affects corneal sensitivity, related to neurotrophic keratopathy, a condition linked to dry eye disease. Although specific safety data for this trial's treatment is not yet available, the long history of dry eye treatments supports their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for neurotrophic keratopathy, which typically include lubricating eye drops or protective contact lenses to manage symptoms, the new treatment for Dry Eye Disease targets the underlying nerve damage causing the condition. Researchers are excited about this approach because it aims to regenerate corneal nerves, potentially offering a more permanent solution rather than just temporary relief. This innovative mechanism of action could lead to significant improvements in vision and comfort for patients who haven't found success with existing therapies.

What evidence suggests that this treatment might be an effective treatment for Neurotrophic Keratopathy?

Research shows that treating Dry Eye Disease (DED) can prevent further eye problems, such as corneal ulcers and scarring, and improve patients' quality of life. Studies highlight the importance of early detection and treatment. For those with DED, maintaining a stable tear film—a thin layer of tears covering the eye—is crucial to avoid irritation and damage. Evidence suggests that some treatments for DED might also help with neurotrophic keratopathy (NK), a condition where the eye loses feeling, and might even aid in repairing nerve damage in the eye. Overall, addressing DED is vital for maintaining eye health and preventing complications. ^{1 2 3 4 6}

Who Is on the Research Team?

John Hovanesian, M.D.

Principal Investigator

Harvard Eye Associates

Are You a Good Fit for This Trial?

This trial is for individuals with Stage 1 Neurotrophic Keratopathy (NK), a condition affecting the cornea and associated with Dry Eye Syndrome. The study aims to identify those who might need future treatment for optimal vision.

Inclusion Criteria

I understand and can sign the consent form.

Patients with central or inferior corneal fluorescein staining defined by the Oxford Scale

I can attend all follow-up appointments after surgery.

Exclusion Criteria

Moderate to severe allergic, vernal or giant papillary conjunctivitis

Participation in this trial in the same patient's fellow eye

Ocular inflammation at the discretion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Evaluation of corneal sensitivity and clinical parameters in patients with signs of dry eye disease

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after baseline assessment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dry Eye Disease

Trial Overview

The THINK Study focuses on evaluating corneal sensitivity in patients with early-stage NK to predict the necessity of rhNGF, a treatment that may be required for maintaining good visual performance.

How Is the Trial Designed?

Group I: Dry Eye Disease Experimental Treatment 1 Intervention

Patients who have signs of dry eye

Dry Eye Disease is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Dry Eye Disease for:

• Dry Eye Syndrome
• Keratoconjunctivitis Sicca

Approved in European Union as Dry Eye Disease for:

• Dry Eye Syndrome
• Keratoconjunctivitis Sicca

Approved in Canada as Dry Eye Disease for:

• Dry Eye Syndrome
• Keratoconjunctivitis Sicca

Approved in Japan as Dry Eye Disease for:

• Dry Eye Syndrome
• Keratoconjunctivitis Sicca

Who Is Running the Clinical Trial?

Research Insight LLC

Lead Sponsor

Trials

13

Recruited

900+

Published Research Related to This Trial

Dry eye disease is primarily caused by either reduced tear production or increased tear evaporation, leading to discomfort and potential damage to the ocular surface.

Understanding the different types of dry eye is crucial for proper diagnosis and management, as symptoms can sometimes mimic other conditions like lacrimal drainage disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The "wet" dry eye]. Schargus, M., Geerling, G.[2021]

Dry Eye Disease (DED) is a complex condition characterized by discomfort and visual disturbances, categorized into aqueous-deficient dry eye and evaporative dry eye, requiring a thorough diagnostic approach that includes various tests like tear film analysis and osmolarity evaluation.

Treatment for DED varies based on severity and underlying causes, with options including lubricating artificial tears and immunomodulatory agents to address inflammation and restore tear film stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Pharmacology of Tear Film, Dry Eye, and Allergic Conjunctivitis. Gulati, S., Jain, S.[2022]

LASIK surgery has become the standard for correcting refractive errors, with a significant reduction in both intraoperative and postoperative complications over the years.

The most common postoperative issues include keratitis punctata superficialis and dry eye symptoms, which may arise from decreased corneal sensitivity due to nerve cutting during the procedure, highlighting the need for careful management and treatment with artificial tears.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy]. Breil, P., Frisch, L., Dick, HB.[2019]

Dry Eye disease is a common and complex condition characterized by inflammation, loss of tear film stability, and sensory abnormalities, requiring a multifaceted approach for diagnosis and treatment.

Effective management of Dry Eye involves a thorough assessment using various diagnostic tools, including patient symptom scores, slit lamp examinations, and tests for tear secretion and ocular surface inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is Important in Diagnosing Dry Eye Disease - Recommendations According to current Guidelines (DEWS II, DOG/BVA)]. Jacobi, C.[2022]

Keratoconjunctivitis sicca (KCS), a common condition in patients with Sjögren's syndrome, involves not just reduced tear production but also harmful changes to the eye's surface cells, leading to varying symptoms of dryness and discomfort.

Moisturizing eyedrops are highly effective in treating dry eyes in KCS patients, and understanding the underlying causes of decreased tear flow and surface disturbances is crucial for improving treatment strategies, including the use of anti-inflammatory medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular manifestations of Sjögren's syndrome: keratoconjunctivitis sicca. Friedlaender, MH.[2005]

Dry eye disease is a complex condition that involves not just a lack of tears, but also issues with tear quality, epithelial health, and immune responses, highlighting the need for a comprehensive understanding of the ocular surface anatomy.

Recent findings suggest that inflammation, regulated by the eye's immune system, plays a crucial role in the development of dry eye disease, indicating that targeting immune responses may be key in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dry eye disease as a complex dysregulation of the functional anatomy of the ocular surface. New concepts for understanding dry eye disease]. Knop, E., Knop, N., Brewitt, H.[2018]

LASIK surgery, while effective for correcting refractive errors like myopia and astigmatism, can lead to iatrogenic dry eye syndrome due to changes in the cornea and tear film.

The primary treatment for the resulting dry eye condition is the use of artificial tears, as the condition is linked to neurogenic and inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry eye disease after LASIK. Turu, L., Alexandrescu, C., Stana, D., et al.[2021]

A comprehensive review of dry eye therapies revealed that many treatments lack strong evidence (Level 1) to support their use, often due to issues like inadequate study design and small sample sizes.

The review led to the development of a staged management algorithm that emphasizes the importance of distinguishing between aqueous-deficient and evaporative dry eye disease to guide treatment choices, highlighting the need for more robust evidence to improve management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TFOS DEWS II Management and Therapy Report. Jones, L., Downie, LE., Korb, D., et al.[2022]

Dry eye syndrome (DES) is a complex condition affecting the tear film and ocular surface, leading to various symptoms and requiring a combination of subjective assessments for diagnosis.

The article introduces a new technique for assessing tear film stability, which could provide a more objective method for diagnosing DES compared to existing subjective tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current methods of tear film stability assessment]. Safonova, TN., Sikach, EI., Ozheredov, IA.[2020]

A new consensus definition of dry eye disease (DED) has been established, emphasizing it as a multifactorial condition characterized by unstable tear film, inflammation, and ocular discomfort, which aids in consistent diagnosis across practitioners.

This definition also highlights the importance of assessing ocular surface epitheliopathy and neurosensory abnormalities, which can improve the quality of clinical trials and research related to DED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining Dry Eye from a Clinical Perspective. Tsubota, K., Pflugfelder, SC., Liu, Z., et al.[2021]

Dry eye disease (DED) is a complex condition affecting the tear film and ocular surface, leading to discomfort and potential damage, but there are currently no standardized diagnostic criteria for it.

The article reviews the anatomy and physiology of the tear system, the causes and classifications of DED, and highlights the importance of symptom assessment and specific diagnostic tests in identifying the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry eye disease: pathophysiology, classification, and diagnosis. Perry, HD.[2008]

Dry eye is a common complication following LASIK surgery, primarily caused by damage to the corneal nerves, which can lead to further ocular surface damage if not addressed promptly.

Recent studies highlight the importance of early identification and treatment of post-operative dry eye, and introduce advanced evaluation technologies like SD-OCT and corneal confocal microscopy to improve diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in laser in situ keratomileusis-associated dry eye. Xie, W.[2016]

Dry eye disease (DED) affects a significant portion of the population, with its treatment now involving a combination of artificial tears, lid hygiene, and occlusion methods for severe cases, reflecting a shift from just tear substitution to a more comprehensive therapeutic approach.

Long-term use of topical anti-inflammatory treatments, such as corticosteroids and cyclosporine A, has been shown to be effective for moderate to severe dry eye disease, supported by high-level clinical trial evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pathophysiology, diagnosis, and treatment of dry eye disease. Messmer, EM.[2022]

Almost all patients experience some level of dry eye symptoms after LASIK surgery, highlighting the need for better understanding and management of this common complication.

Improving preoperative screening for patients at risk of dry eye can enhance patient satisfaction and lead to better visual outcomes after the surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry Eye Post-Laser-Assisted In Situ Keratomileusis: Major Review and Latest Updates. Cohen, E., Spierer, O.[2020]

Keratoconjunctivitis sicca (KCS), commonly known as dry eye syndrome, is characterized by issues with tear production, quality, or evaporation, leading to discomfort and potential damage to the eye surface.

Symptoms of KCS include irritation, a sensation of a foreign body in the eye, and redness, highlighting the importance of understanding and treating this condition to improve patient comfort and eye health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the treatment of chronic dry eye disease. Sheppard, JD.[2018]

Citations

1.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK470411/

Dry Eye Syndrome - StatPearls - NCBI Bookshelf - NIH

Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms.

2.

emedicine.medscape.com

emedicine.medscape.com/article/1210417-overview

Dry Eye Disease (Keratoconjunctivitis Sicca)

Early detection and aggressive treatment of DED may help prevent corneal ulcers and scarring, as well as improve quality of life metrics.

3.

eyeworld.org

eyeworld.org/2025/identifying-different-types-of-dry-eye/

Identifying different types of dry eye

Lacripep may also possess neuroregenerative properties and efficacy in neurotrophic keratopathy, a comorbidity often seen in severe cases of DED ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0928098722000914

Current trends in pharmaceutical treatment of dry eye ...

This review highlights the etiologies, the pathophysiology of DED, and the role of diagnostic techniques in the policy of treatment.

5.

aaojournal.org

aaojournal.org/article/S0161-6420(24)00012-5/pdf

Dry Eye Syndrome Preferred Practice Pattern®

Dry eye may compromise results of cataract, corneal, and keratorefractive surgery. Clinical examination is the gold standard for diagnosing dry ...

6.

mdpi.com

mdpi.com/1648-9144/61/3/460

Overview of Dry Eye Disease for Primary Care Physicians

If left untreated, DED holds the risk for long-term consequences such as chronic inflammation leading to tissue damage and scarring in the visual axis and ...