The Effect Of High And Low Molecular Weight Sodium Hyaluronic Acid Eye Drops After Crosslinking

Keratoconus Clinical Trial

Official title:

The Effect Of High And Low Molecular Weight Sodium Hyaluronic Acid Eye Drops On Corneal Recovery After Crosslinking

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06243991
• Other study ID #: 09.2021.86
• Status: Completed
• Start date: March 1, 2021
• Est. completion date: February 1, 2023

Study information

• Verified date: January 2024
• Source: Marmara University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Purpose: The objective of this investigation was to assess the impact of eye drops containing high molecular weight hyaluronic acid (HMW-HA) and low molecular weight hyaluronic acid (LMW-HA) on corneal nerve regeneration, dendritic cell (DC) density, corneal sensitivity (CS), and ocular surface parameters in patients with keratoconus following corneal crosslinking (CXL). Methods: Sixty-three eyes of 55 keratoconus patients were randomized to instill eye drops containing HMW-HA (n: 20) for 12 months, LMW-HA (n:23) for 12 months and polyvinyl alcohol (n: 20) until the epithelial defect closure in the control group after CXL. Subbasal nerve plexsus (SNP) was imaged with corneal confocal microscopy (CCM) and ACCMetrics program was used to quantify corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve fiber branching density (CNBD) and corneal nerve fiber total branching density (CTBD). DC density was calculated with Image J software. CS was measured using the Cochet-Bonnet esthesiometer. Ocular Surface Disease Index (OSDI) questionnaire, non-invasive break-up time (NI-TBUT) were evaluated. All measurements were performed before CXL and postoperatively after 1, 3, 6 and 12 months.

Description:

This study assessed individuals aged 18 and above diagnosed with keratoconus and scheduled for epithelium-off CXL. A total of 63 eyes from 55 keratoconus patients were randomly assigned using computer-generated randomization (www.random.org/integers) into three groups: 20 eyes in the HMW-HA group, 23 eyes in the LMW-HA group, and 20 eyes in the control group without the administration of artificial tears. Post-CXL, the HMW-HA group received topical HMW-HA (Comfort Shield®, i.com medical GmbH, Munich, Germany) three times daily for 12 months, the LMW-HA group received topical LMW-HA (Thealose Duo®, Thea, Clermont-Ferrand, France) three times daily for 12 months, and the control group received topical polyvinyl alcohol (Refresh, Allergan, Dublin, Ireland) three times daily until epithelial defect closure. All participants underwent accelerated epithelium-off CXL (A-CXL) for 10 minutes with 9 mW/cm² ultraviolet-A irradiation. The postoperative standard treatment regimen included topical moxifloxacin (0.5% Vigamox, Alcon Inc, USA) for one week, topical dexamethasone (0.1% Dexasine-SE, Kaysersberg Pharmaceuticals, France) for one week after epithelial closure, followed by topical loteprednol 0.5% (Lotemax, Bausch & Lomb, USA) for three weeks. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and manifest spherical equivalent (SE) were recorded at all visits. The assessment was carried out in the following order: Ocular Surface Disease Index (OSDI) questionnaire, noninvasive tear break-up time (NIBUT), corneal tomography (Pentacam, OCULUS, Wetzlar, Germany), corneal sensitivity, corneal fluorescein staining, and CCM imaging. Examinations were conducted preoperatively and at the postoperative 1th, 3rd, 6th and 12th months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: February 1, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Keratoconus patiens aged 18 and above who had been scheduled for corneal crosslinking

Exclusion Criteria:

• Dry eye disease, corneal thickness below 400 micrometer, pregnancy, breastfeeding, topical or systemic drug use, eye disease other than keratoconus, systemic diseases, active atopy or allergy, contact lens use, ocular surgery history.

Related Conditions & MeSH terms

• Keratoconus

Intervention

Device:
• in vivo Corneal Confocal Microscopy
CCM was performed using the Heidelberg Retinal Tomograph 3 with the Rostock Cornea Module (HRT3-RCM, Heidelberg Engineering GmbH, Germany) under topical anesthesia. A viscous gel (Viscotears, Novartis Pharmaceuticals UK) served as a coupling agent between the cornea and the applanation cap. The subjects were instructed to focus on the fixation light with the unexamined eye to ensure proper positioning. Five high-quality images of the SNP were selected and analyzed using the automated tracing of nerve fibers program (ACCMetrics, M.A. Dabbah, Imaging Science and Biomedical Engineering, Manchester, England).

Diagnostic Test:
• Corneal Sensitivity
Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer (Luneau Ophtalmologue, Chartres, France), comprising a nylon filament measuring 60 mm in length and 0.12 mm in diameter. Participants were instructed to maintain a forward gaze while the esthesiometer gently made perpendicular contact. The procedure involved gradually decreasing the filament length in 5 mm increments, starting from 60 mm, until the initial response from the subject was detected.

Device:
• Non invasive tear break up time
Noninvasive tear break-up time (NI-TBUT) was assessed using a Sirius Scheimpflug camera (CSO, Florence, Italy) and the device automatically provided the average NI-TBUT value

Diagnostic Test:
• Ocular Surface Disease Index Qestionnaire
The Ocular surface disease index (OSDI) questionnaire consists of a total of 12 questions categorized into three subscales as follows: ocular symptoms, vision-related function, and environmental triggers. Each patient is asked to rate the symptoms on a 5-point scale ranging from never (0 score) to always (4 score) for every question in the questionnaire. The fourth and fifth questions in the first section, concerning blurred vision and reduced vision symptoms, were excluded from the questionnaire as these symptoms may already be present in patients with keratoconus disease. The total OSDI score was calculated according to the formula: OSDI = [(sum of scores for all questions answered) × 100] / [(total number of questions answered) × 4].

Device:
• Corneal tomography
Scheimpflug-tomography device (Pentacam, OCULUS, Wetzlar, Germany) was used for measurement of keratometric values.

Locations

Country	Name	City	State
Turkey	Marmara University	Istanbul	Pendik

Sponsors (1)

Lead Sponsor	Collaborator
Marmara University

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Corneal nerve fiber density (CNFD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFD.	Baseline
Primary	Corneal nerve fiber density (CNFD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFD.	Postoperative 1st, 3rd, 6th and 12th months
Primary	Corneal nerve branch density (CNBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNBD.	Baseline
Primary	Corneal nerve branch density (CNBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNBD.	Postoperative 1st, 3rd, 6th and 12th months
Primary	Corneal nerve fiber length (CNFL)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFL	Baseline
Primary	Corneal nerve fiber length (CNFL)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CNFL	Postoperative 1st, 3rd, 6th and 12th months
Primary	Corneal nerve fiber total branching density (CTBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CTBD.	Baseline
Primary	Corneal nerve fiber total branching density (CTBD)	Automated tracing of nerve fibers program - CCMetrics (CCMetrics; M. A. Dabbah, ISBE, University of Manchester, Manchester, UK) was used to analyze CTBD.	Postoperative 1st, 3rd, 6th and 12th months
Primary	Corneal Sensitivity	Corneal sensitivity was assessed using a Cochet-Bonnet esthesiometer (Luneau Ophtalmologue, Chartes, France).	Baseline
Primary	Corneal Sensitivity	Corneal sensitivity was assessed using a Cochet-Bonnet esthesiometer (Luneau Ophtalmologue, Chartes, France).	Postoperative 1st, 3rd, 6th and 12th months
Primary	Dendritic cell density	The Density of dendritic cells was calculated using ImageJ software (Image V.1.31; National Institutes of Health)	Baseline
Primary	Dendritic cell density	The Density of dendritic cells was calculated using ImageJ software (Image V.1.31; National Institutes of Health)	Postoperative 1st, 3rd, 6th and 12th months
Primary	Ocular surface disease Index (OSDI) questionnaire	The Turkish validated version of the OSDI, a questionnaire assesing the clinical symptoms of the ocular surface disease, was used. The 4th and 5th questions in the first section, which inquire about blurred vision and reduced vision symptoms, were excluded from the questionnaire as they could already be present in patients with keratoconus disease.	Baseline
Primary	Ocular surface disease Index (OSDI) questionnaire	The Turkish validated version of the OSDI, a questionnaire assesing the clinical symptoms of the ocular surface disease, was used. The 4th and 5th questions in the first section, which inquire about blurred vision and reduced vision symptoms, were excluded from the questionnaire as they could already be present in patients with keratoconus disease.	Postoperative 1st, 3rd, 6th and 12th months
Primary	Non invaziv tear break-up time (NI-TBUT)	The tear break-up time (TBUT) was evaluated non-invasively using a Sirius Scheimpflug camera (CSO, Florence, Italy).	Baseline
Primary	Non invaziv tear break-up time (NI-TBUT)	The tear break-up time (TBUT) was evaluated non-invasively using a Sirius Scheimpflug camera (CSO, Florence, Italy).	Postoperative 1st, 3rd, 6th and 12th months
Secondary	Visual Functions	Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA) by the Snellen chart, based on the logMAR scoring system and manifest spherical equivalent (SE) were assessed.	Baseline
Secondary	Refractive Outcomes	Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA) by the Snellen chart, based on the logMAR scoring system and manifest spherical equivalent (SE) were assessed.	Postoperative 1st, 3rd and 6th months
Secondary	Keratometric Findings	Corneal tomography (Pentacam, OCULUS, Wetzlar Germany) was used to obtain the data for K1, K2, Kmean, Kmax, and the Thinnest point (TP).	Baseline
Secondary	Keratometric Findings	Corneal tomography (Pentacam, OCULUS, Wetzlar Germany) was used to obtain the data for K1, K2, Kmean, Kmax, and the Thinnest point (TP).	Postoperative 1st, 3rd and 6th months