Dry Eye Disease for Neurotrophic Keratopathy

(THINK Trial)

Overseen by John Hovanesian, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Research Insight LLC

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

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The study purpose is to evaluate corneal sensitivity in patients that have Stage 1 Neurotrphic Keratopathy (NK). Identifying patients with Stage 1 NK, may predict those who will in the future require rhNGF for optimal visual performance.

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 data supports the effectiveness of the treatment for Dry Eye Disease in Neurotrophic Keratopathy?

The research suggests that moisturizing eyedrops, which are commonly used to treat dry eyes, are effective in providing relief for patients with dry eye symptoms, including those with keratoconjunctivitis sicca (a type of dry eye condition). However, more evidence is needed to fully support the effectiveness of many treatments for dry eye disease, as current studies often lack strong evidence due to issues like small sample sizes or lack of proper controls. ^{1 2 3 4 5}

Is the treatment for dry eye disease and related conditions generally safe for humans?

The treatment for dry eye disease, especially after LASIK surgery, is generally considered safe, with the main therapy involving the use of artificial tears to manage symptoms. Complications have decreased over time with improved surgical techniques and postoperative care. ^{6 7 8 9 10}

How is this treatment for Dry Eye Disease different from other treatments?

This treatment for Dry Eye Disease is unique because it specifically targets neurotrophic keratopathy, a condition where the cornea loses its ability to sense and respond to stimuli, which is not typically addressed by standard dry eye treatments like artificial tears or anti-inflammatory medications. ^{11 12 13 14 15}

Research Team

John Hovanesian, M.D.

Principal Investigator

Harvard Eye Associates

Eligibility Criteria

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.

I can attend all follow-up appointments after surgery.

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

Exclusion Criteria

Moderate to severe allergic, vernal or giant papillary conjunctivitis

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

I am not under 18, pregnant, breastfeeding, or planning to become pregnant.

Trial Timeline

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

Treatment Details

Interventions

• Dry Eye Disease (Neurotrophic Keratopathy)

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.

Participant Groups

Group I: Dry Eye Disease Experimental Treatment 1 Intervention

Patients who have signs of dry eye

Dry Eye Disease is already approved in Canada, Japan for the following indications:

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+

Findings from Research

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), 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]

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]

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 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]

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 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 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]

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]

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]

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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

TFOS DEWS II Management and Therapy Report. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Current methods of tear film stability assessment]. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. Germany 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]. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

[Diagnosis and therapy of LASIK-induced neurotrophic epitheliopathy]. [2019]

9. Romania pubmed.ncbi.nlm.nih.gov

Dry eye disease after LASIK. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Dry Eye Post-Laser-Assisted In Situ Keratomileusis: Major Review and Latest Updates. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Defining Dry Eye from a Clinical Perspective. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

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

13. Germany pubmed.ncbi.nlm.nih.gov

[The "wet" dry eye]. [2021]

14. Germany pubmed.ncbi.nlm.nih.gov

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

15. Germany pubmed.ncbi.nlm.nih.gov

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