Clinical trial NCT06202651: Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) Laser Treatment for Granular Corneal Dystrophy
Official title: Treatment of Granular Corneal Dystrophy Using Nd-YAG Laser
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Granular Dystrophy, Corneal
Keywords: Granular Dystrophy
Cornea
Nd:YAG Laser
Neodymium-doped Yttrium Aluminum Garnet Laser
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2024-01-11
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single interventional group of Granular Corneal Dystrophy participants over the age of 18 years that undergo a single Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) Laser treatment.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: Granular Corneal Dystrophy is a rare hereditary disease characterized by the development of deposits within the cornea, which may in turn affect the quality of vision. Still today, all existing treatment options are based on surgical intervention and there is no minimally-invasive treatment available for the disease.

The goal of this clinical trial is to test the effectiveness and safety of Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser as a minimally-invasive treatment for people suffering from Granular Corneal Dystrophy. The main question it aims to answer is if Nd:YAG laser is able to disintegrate the characteristic corneal depositions in a safe manner without causing significant adverse effects.

If found suitable to be part of the study, participants will first undergo a series of imaging studies to measure and characterize the corneal deposits. After completion, the participants will undergo the Nd:YAG laser treatment under local anesthesia by a corneal specialist, targeting deposits not involving the visual axis. Following the treatment, participants might need to take antibiotic eye drops for a duration of approximately one week. The participants will be required to attend two follow-up visits: one week after the treatment and 3 months after the treatment. In each one of the follow-up visits, an eye examination will be performed and the same series of imaging studies that was performed prior to the Nd:YAG laser treatment will be repeated.

Detailed description: Neodymium:yttrium aluminum garnet (Nd:YAG) laser is an ophthalmic instrument that finds versatile use in clinical practice since its first introduction in 1980s. This solid-state laser emits infrared light at a wavelength of 1064 nm that can disrupt ocular tissues by causing an optical breakdown with a short, high-power pulse. Thanks to its high precision, minimal-invasive mode of delivery, and well-established safety profile, its application ranges from treatment of posterior capsule opacification, chronic and acute angle-closure glaucoma, vitreous floaters, to proliferative diabetic retinopathy.

Granular corneal dystrophy (GCD) is a rare hereditary condition characterized by progressive deposition of insoluble protein aggregates in the cornea. The small, white-greyish granular deposits typically begin to form during childhood and grow in size and number with increasing age, eventually coalescing and causing significant visual impairment.

Still today, there is no minimal-invasive treatment available for GCD patients. Current treatment approaches include partial or full-thickness corneal transplant, which is associated with a relatively high recurrence rate and potentially sight-threatening complications. In addition, there is a global shortage of available donor corneas. Therefore, there is an unmet need for a minimal-invasive treatment that could reduce this indication for corneal transplantation and provide symptomatic relief to GCD patients.

As modern Nd:YAG laser systems can focus on a spot size as small as 8-10 µm in different depths of the cornea, the study team hypothesize that the Nd:YAG laser would be capable of accurately targeting the GCD deposits and serve as a viable minimal-invasive treatment option for this disease.

Hence, in the proposed research, the investigators seek to evaluate the efficacy and safety of the Nd:YAG laser in the treatment of GCD patients. If found to be efficacious and safe, the investigators hypothesize that GCD patients will benefit from both the minimal-invasive form of treatment and prompt improvement in quality of life and vision.

During the study, as part of the initial assessment, the participants will undergo routine ophthalmic examination including visual acuity testing, slit-lamp examination, intra-ocular pressure measurement, and corneal imaging including Scheimpflug tomography (Pentacam®), anterior-segment optical coherence tomography (AS-OCT), and slit-lamp photography of the cornea (visit 1). All the above imaging modalities are non-contact, take seconds to perform, and represent no risk to the participant.

Following the initial assessment, the Nd:YAG laser procedure will be performed on the same day (visit 1) or on a separate date (visit 2) depending on the time schedule of both the participant and the research team. One eye will be included in the study per participant. If the severity of the disease is asymmetrical, the eye with more extensive corneal deposition will be included. If the severity is symmetrical, the participant's non-dominant eye will be included as determined by the standard dominance testing method.

Using the slit-lamp, the primary investigator, a corneal specialist, will find the two most peripheral deposits that are of ca. 50 µm size. The width of the thinnest slit-lamp beam, which is 1 mm, will be used as a guide to estimate the deposits' size. The exact size of each opacity will be measured using the images taken by the AS-OCT and slit-lamp photography.

Prior to the Nd:YAG laser treatment, two drops of topical anesthetic will be administered to the study eye to anesthetize the eye, as is always done prior to any other Nd:YAG procedure. The treatment will be delivered using an Optimis II device (Quantel Medical). This is an FDA-approved device used regularly for other ocular indications, that due to its adherence to Non-Significant Risk (NSR) criteria, received an abbreviated Investigational Device Exemption (IDE) approval by the institutional review board (IRB) for the purpose of this study. Typically, a single-pulse Nd:YAG laser energy levels of 2-3 mJ is sufficient to treat posterior capsule opacification, while 2-8 mJ of energy is used to perform an iridotomy. In this research, the primary investigator will begin with the lowest energy setting (0.3 mJ) and increase the energy levels to 3 mJ in increments of 0.5 mJ. Five single-burst shots will be performed per laser energy setting per opacity until a visible effect is seen.

After the procedure, the eye will be examined to assess the integrity of the corneal epithelium. If a defect is seen, the participant will be advised to administer topical antibiotic eye drops three times daily for a week as a precautionary measure. The investigators hypothesize minor risks of corneal scarring or intraocular inflammation after the laser treatment. The participants' visual acuity should not be affected as only peripheral deposits that lie outside the visual axis will be subjected to treatment in this research.

The participant will return one week (visit 2 or 3) and three months (visit 3 or 4) later for follow-up at which the participant will repeat the clinical examination and imaging studies included above. The study cornea will be examined carefully for any signs of inflammation or scarring. The size of the opacities that were treated with Nd:YAG laser will be re-measured using the images taken by the anterior-segment OCT and slit-lamp photography. After the last follow-up examination, the participants will be referred to routine care.

During the entire course of the study, confidentiality will be ensured using standard procedures including storage of study data on password protected computers utilizing a Secure Analytic Framework Environment (SAFE) desktop. Participants will be assigned study identification codes that will be used for all subsequent study procedures.

Eligibility criteria: Inclusion Criteria:

* Patients older than 18 years of age
* Diagnosis of granular corneal dystrophy with presence of granular opacities in the peripheral cornea of appropriate size (ca. 50 µm) in at least one eye
* Willingness and ability to give signed informed consent and follow study instructions

Exclusion Criteria:

* Presence of any active intra-ocular inflammation
* Pre-existing glaucoma or retinal edema
* Cannot properly self-administer or receive an eye drop medication

Primary outcomes:
measure: Change in size of granular corneal deposits due to Nd:YAG laser treatment
timeFrame: Baseline, Post-intervention day 7, Post-intervention 3 months
Secondary outcomes:
measure: Safety as the number participants experiencing adverse events of inflammation and/or scarring
timeFrame: Post-intervention day 7, Post-intervention 3 months
measure: Safety as the number of participants experiencing decrease in visual acuity
timeFrame: Baseline, Post-intervention day 7, Post-intervention 3 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Wilmer Eye Institute - Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Wilmer Eye Institute/Johns Hopkins University
name: Albert S Jun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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