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.