Biomarker Sampling for Glaucoma Detection

(AH-Tears Trial)

Overseen By Dominique Geoffrion, B.Sc.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Other ocular diseases

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

Compensation: Varies

Number of Visits: 7

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Glaucoma is the most common threat to vision rehabilitation in patients with Boston keratoprosthesis type 1 (KPro) implantation. High intraocular pressure (IOP) is the most important risk factor for glaucoma and may lead to irreversible retinal and optic nerve damage. Glaucoma drainage device (GDD) surgery is used to divert aqueous humor (AH) from the anterior chamber to an external reservoir to regulate flow and decrease the IOP. The AH is in direct communication with any corneal damage or surgery undertaken in the anterior chamber and can serve as a source of potential biomarkers to detect early inflammatory or glaucomatous changes. Tears are also one of the most accessible and non-invasive source of biomarkers, especially in Kpro eyes where the central optic allows communication between aqueous humor and the tears at the surface of the eye. The investigators propose to test the hypothesis that distinct inflammatory mediators in the AH and tears can serve as biomarkers for glaucoma development and progression after CT, making them specifically amenable to targeted treatment strategies to minimize vision loss.

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of the treatment involving sampling of aqueous humor and tears for glaucoma detection?

Research shows that analyzing tear fluid can help identify specific markers related to glaucoma, which can aid in early diagnosis. This approach is promising because it allows for minimally invasive sampling and can provide sensitive and rapid detection of glaucoma. ^{1 2 3 4 5}

Is tear sampling safe for humans?

Tear sampling methods, such as using phenol red threads and polyethylene tubes, are considered low in invasiveness and discomfort, making them safe for human use. These methods do not significantly alter the chemical composition of the tears, ensuring reliable research results without causing harm to the eye. ^{6 7 8 9 10}

How does this treatment for glaucoma differ from others?

This treatment is unique because it focuses on analyzing tear fluid to identify specific biomarkers for early glaucoma detection, which is different from traditional methods that often rely on symptom observation or eye pressure measurement. ^{1 3 9 11 12}

Research Team

Younes Agoumi, MD FRCSC

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Mona Harissi-Dagher, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for adults over 18 who can be monitored throughout the study. It's suitable for those needing corneal transplants, with or without glaucoma, and those requiring glaucoma surgery, with prior corneal transplants. Participants must have specific eye conditions and give informed consent. Those under 18 or unable to consent, or with other eye diseases are excluded.

Inclusion Criteria

You understand and agree to participate in the study after being provided with all the necessary information.

I do not have glaucoma or any systemic diseases.

I have the eye condition specified for my group.

Exclusion Criteria

I am under 18 years old.

I am unable to understand and give consent for treatment.

I have eye conditions not being studied in this trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Corneal Transplantation

Participants undergo corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis) and samples are collected at baseline

Baseline

1 visit (in-person)

Intraocular Surgery

Participants undergo intraocular surgery (cataract, retina, or glaucoma) following corneal transplantation, with sample collection for analysis

3-12 months

Multiple visits (in-person) at 3, 6, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of intraocular pressure and structural changes

12 months

Regular visits (in-person) at 3, 6, and 12 months

Treatment Details

Interventions

• Sampling of aqueous humor
• Sampling of tears

Trial Overview The study investigates if certain inflammatory substances in the fluid (aqueous humor) inside the eye and tears can predict glaucoma after a corneal transplant. Researchers will collect samples of this fluid and tears from participants to identify potential biomarkers.

Participant Groups

Group I: Intraocular surgery following corneal transplantation Experimental Treatment 2 Interventions

Participants needing intraocular surgery (cataract, retina or glaucoma), with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis). This allows analyzing samples during the potential development or progression of glaucoma in participants who have previously undergone corneal transplantation.

Group II: Glaucoma surgery following corneal transplantation Experimental Treatment 2 Interventions

Participants needing glaucoma filtration surgery, with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis). This allows analyzing samples once glaucoma is confirmed in participants who have previously undergone corneal transplantation.

Group III: Corneal transplantation Experimental Treatment 2 Interventions

Participants needing corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis), with or without glaucoma. This allows analyzing samples at baseline (time 0), at the time of the corneal transplantation procedure.

Group IV: Cataract surgery only Placebo Group 2 Interventions

Participants needing cataract surgery, without glaucoma or any other corneal diseases.

Group V: Glaucoma surgery only Placebo Group 2 Interventions

Participants needing glaucoma filtration surgery, without any prior corneal transplantation.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

Tear fluid analysis is a promising method for identifying new biomarkers for early diagnosis of glaucoma, which is crucial since the disease often progresses without symptoms until advanced stages.

Identifying specific and sensitive biomarkers in tear fluid could help in understanding the underlying mechanisms of glaucoma and differentiate between its various types, potentially leading to better diagnostic and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tear Film-specific Biomarkers in Glaucoma Patients. Fomo, KN., Schmelter, C., Pfeiffer, N., et al.[2022]

The study developed a novel method using three-dimensional synchronous fluorescence spectroscopy (3D-SFS) to analyze tear fluid, which can help distinguish between healthy individuals and those with primary open-angle glaucoma (POAG).

By processing synchronous excitation spectra and utilizing second derivative analysis, the researchers identified key parameters that improve the diagnostic accuracy for early-stage glaucoma, suggesting potential for machine learning applications in automated diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Derivative Three-Dimensional Synchronous Fluorescence Analysis of Tear Fluid and Their Processing for the Diagnosis of Glaucoma. Dubayová, K., Krajčíková, K., Mareková, M., et al.[2022]

In patients with glaucoma undergoing chronic topical treatments, there is a significant increase in pro-inflammatory cytokines in their tears, indicating an inflammatory response to the medication.

The study found that both Th1 and Th2 type cytokines were elevated, with Th1 cytokines showing the most marked increase, suggesting that these treatments may provoke an immune response that could affect ocular surface health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. Malvitte, L., Montange, T., Vejux, A., et al.[2018]

Biomarkers are valuable tools for understanding ocular diseases, aiding in diagnosis, treatment monitoring, and predicting clinical responses, thanks to their ability to provide measurable indicators of disease processes.

The review highlights the use of easily accessible ocular matrices like tears and aqueous humor for biomarker evaluation, which allows for repeat sampling and objective measures of treatment effectiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Biomarkers in Ocular Matrices: Challenges and Opportunities. Tamhane, M., Cabrera-Ghayouri, S., Abelian, G., et al.[2020]

In a study of 33 young adults, significant changes in eye aberrations were observed during the 10 seconds after blinking, indicating that the tear film's stability can affect visual quality.

The research found that individuals with shorter tear film break-up times (TFBUTs) exhibited greater wavefront aberrations, suggesting that tear quality may play a crucial role in eye health and vision, highlighting the need for personalized assessments in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic changes in ocular Zernike aberrations and tear menisci measured with a wavefront sensor and an anterior segment OCT. Xu, J., Bao, J., Deng, J., et al.[2019]

In a study involving 15 subjects, different tear collection methods were compared, revealing that Schirmer's strip collection provided the highest concentration of MUC5AC, while basal tear collection yielded the highest concentration of MUC16.

The findings suggest that the choice of tear collection method should be based on the specific mucin being analyzed, as each method has distinct advantages for capturing different mucins in human tear fluid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentrations of MUC16 and MUC5AC using three tear collection methods. Ablamowicz, AF., Nichols, JJ.[2022]

The newly designed tear collection apparatus allows for the collection of larger volumes of tears quickly and safely, minimizing the risk of damaging the eye, which enhances the reliability of tear chemistry research.

This method not only preserves the chemical composition of the tear samples but also reduces irritation for subjects, making it easier to gather larger participant groups for studies on eye diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An improved technique for collection of human tears. Webster, HJ., Kairys, DJ.[2018]

In a clinical trial evaluating three topical ophthalmic medications, 957 volunteers were recruited, but only 320 were enrolled due to strict eligibility criteria, primarily related to abnormal tear production as measured by the Schirmer test.

The study found that 22% of screened subjects had abnormal Schirmer test results, with decreased tear production being the most common issue, highlighting the importance of screening in clinical trial design for ophthalmic studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recruitment and screening experience for a clinical trial involving tear concentrations of a new drug. D'Antonio, JA., Baker, KS., Berkebile, CE., et al.[2019]

The Schirmer tear test (STT) shows a rapid initial uptake of tears followed by a steady state, allowing for a more detailed understanding of tear production over time, which is crucial for diagnosing conditions like keratoconjunctivitis sicca (KCS).

In normal dogs, the initial tear uptake rate was significantly higher (29.3 mm/min) compared to dogs with KCS (1.9 mm/min), indicating that the STT can effectively differentiate between normal tear production and abnormalities in tear film.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of tear uptake by the Schirmer tear test strip in the canine eye. Williams, DL.[2018]

A novel technique using phenol red threads for collecting human tear samples has been shown to be as effective, if not more so, than traditional methods like glass capillaries and Schirmer's paper strips for proteomic analysis.

This method is low-invasive and causes minimal discomfort to patients, making it a promising option for collecting tear samples to identify biomarkers and monitor treatment effectiveness in eye and systemic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods. Kecskeméti, G., Tóth-Molnár, E., Janáky, T., et al.[2022]

A new method for quantifying tear protein concentration was developed, allowing for sensitive measurement in small tear sample volumes (as low as 3 microL) from healthy subjects, with a mean protein concentration of 4.11 mg/mL.

The assay demonstrated consistent results across samples from 33 healthy individuals, indicating its reliability and potential for use in clinical settings to assess tear protein levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protein dye-binding assay on cellulose membranes for tear protein quantification: use of conventional schirmer strips. López-Cisternas, J., Castillo-Díaz, J., Traipe-Castro, L., et al.[2015]

A study involving 52 glaucoma patients and 55 control subjects identified eight biomarkers in the aqueous humor that can distinguish glaucoma from non-glaucoma controls with 90% sensitivity and 87% specificity, highlighting the potential for early diagnosis.

One significant biomarker, transthyretin, was found to be upregulated in glaucoma patients and may contribute to the disease by forming amyloid deposits that could obstruct fluid outflow and increase intraocular pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transthyretin and complex protein pattern in aqueous humor of patients with primary open-angle glaucoma. Grus, FH., Joachim, SC., Sandmann, S., et al.[2021]

References

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

Tear Film-specific Biomarkers in Glaucoma Patients. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Derivative Three-Dimensional Synchronous Fluorescence Analysis of Tear Fluid and Their Processing for the Diagnosis of Glaucoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. [2018]

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

Review of Biomarkers in Ocular Matrices: Challenges and Opportunities. [2020]

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

Dynamic changes in ocular Zernike aberrations and tear menisci measured with a wavefront sensor and an anterior segment OCT. [2019]

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

Concentrations of MUC16 and MUC5AC using three tear collection methods. [2022]

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

An improved technique for collection of human tears. [2018]

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

Recruitment and screening experience for a clinical trial involving tear concentrations of a new drug. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Analysis of tear uptake by the Schirmer tear test strip in the canine eye. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods. [2022]

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

A protein dye-binding assay on cellulose membranes for tear protein quantification: use of conventional schirmer strips. [2015]

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

Transthyretin and complex protein pattern in aqueous humor of patients with primary open-angle glaucoma. [2021]