A Study to See if Low Level Laser Light Can Help to Treat Toenail Fungus

Nail onychomycosis, or fungus infection, is typically caused by a fungus called
dermatophytes, but may also be caused by yeasts and molds. These microscopic organisms invade
the skin through tiny invisible cuts or through a small separation between the nail and the
nail bed. Under conditions of warmth and moisture, the fungi grow and spread. The infection
begins as a white or yellow spot under the tip of the nail, and as it spreads deeper into the
nail, causes unsightly and potentially painful nail discoloration, thickening and the
development of crumbling edges. Onychomycosis occurs more commonly in toenails than in
fingernails because toenails are often confined in a dark, warm, moist environment inside
shoes where fungi can thrive. Toenail fungus affects approximately 23 million people in the
US - about 10% of all adults.

Potential complications of onychomycosis include pain in the nails, permanent damage to the
nails, development of other serious infections that can spread beyond the feet for
individuals with a suppressed immune system due to medication, diabetes or other conditions,
such as leukemia and AIDS.

Nail fungus can be difficult to treat, and repeated infections are common. Currently
available treatments for onychomycosis include oral antifungal medications, antifungal
lacquer, and topical medications, surgical nail removal and photodynamic therapy. There is no
perfect cure for toenail fungus. Even the most effective oral medications are successful only
about half of the time, and topical medications are successful less than 10% of the time.
Recently, research has found laser therapy to show promise as a novel alternative treatment
for toenail onychomycosis. Unlike medication-driven treatments for toenail fungus which can
have many side effects including serious ones such as liver toxicity, laser therapy presents
minimal to no risk of side effects. Laser therapy is applied to toenail onychomycosis by
shining a laser light through the toenail into the tissue below. The laser light vaporizes
the fungus while leaving the skin and surrounding healthy tissue unharmed.

Low level laser therapy operates under the principle of photochemistry with a photoacceptor
molecule absorbing the emitted photons and inducing a biological cascade. Like our eukaryotic
cell, fungi contain the highly complex organelle the mitochondria, which is responsible for
the manufacturing of the energy molecule adenosine triphosphate (ATP). Within the inner
mitochondrial membrane is cytochrome c oxidase, an identified photoacceptor molecule. It is
believed that laser therapy could perhaps provide a means to photo-destroy the fungi
responsible for onychomycosis (OM) by inducing the release of highly reactive superoxides.
Moreover, laser therapy has been shown to promote superoxide dismutase (SOD), a process
responsible for the destruction of foreign invaders. Extracellular release of low levels of
mediators associated with SOD can increase the expression of chemokines, cytokines, and
endothelial leukocyte adhesion molecules, amplifying the cascade that elicits the
inflammatory response. The physiologic function of hydrogen peroxide, superoxide anion, and
hydroxyl free radical is to destroy phagocytosed microbes. By enhancing the natural processes
of the immune system and impacting the structural integrity of the fungi strain, it is
believed that laser therapy may provide a means for clinicians to effectively treat OM
without the onset of any adverse events.

Inclusion Criteria:

- Visual clinical presentation of onychomycosis in the target great toenail is distal
subungual onychomycosis (DSO), visualized as a nail with normal surface texture and
thickness but variable "bays" of white nail that extend from the distal nail tip
proximally into the area of the nail bed

- Clinical involvement of onychomycosis in the target toenail is up to 60%

- Confirmation of the presence of fungal infection through a positive KOH stain finding
and a positive fungal culture finding

- Identification through fungal culture of the growth of Trichophyton rubrum (T. rubrum)
or other common dermatophyte or C. albicans or mixed dermatophyte/Candida infection.
In the event of the KOH stain and the fungal culture provide conflicting results,
i.e., one is positive and the other negative, resolution may be obtained by a second
negative fungal culture finding from a nail clipping from the same nail

- Subject is willing and able to refrain from employing other (non-study) treatments
(traditional or alternative) for his or her toenail onychomycosis throughout study
participation.

- Subject is willing and able to refrain from the use of nail cosmetics such as clear
and/or colored nail lacquers throughout study participation

Exclusion Criteria:

- Visual clinical presentations of onychomycosis in the target great toenail that are
inconsistent with the clinical presentation of distal subungual onychomycosis (DSO),
in whole or in part (i.e. indicative of mixed etiology); specifically proximal
subungual onychomycosis (PSO); superficial white onychomycosis (SWO); complete
dystrophy; other nail changes.

- Identification through fungal culture of the growth of a rare fungal species (i.e. not
Trichophyton rubrum (T. rubrum) or other common dermatophyte or C. albicans or mixed
dermatophyte/Candida infection) or non-fungal organisms such as mold or bacteria

- Less than 2mm clear (unaffected) nail plate length beyond the proximal fold

- Presence of dermatophytoma (thick masses of fungal hyphae and necrotic keratin between
the nail plate and nail bed)

- Infection involving lunula e.g., genetic nail disorders, primentary disorders

- Severe plantar (moccasin) tinea pedis

- Psoriasis of the skin and/or nails, lichen planus, or other medical conditions known
to induce nail changes

- Onychogryphosis

- Trauma from ill-fitting shoes, running, or overly-aggressive nail care

- Previous toenail surgery

- Uncontrolled diabetes mellitus

- Peripheral vascular disease

- Recurrent cellulitis

- Lymphatic insufficiency

- Immune compromise (whether due to underlying medical disorders or immuno-suppressive
treatments)

- Other compromised states of health

- Known photosensitivity disorder

- Use of oral antifungal drugs in the prior 6 months

- Use of topical treatment of the skin or nails within the prior 2 months

- Any abnormality of the toenail that could prevent a normal appearing nail from
occurring if clearing of infection is achieved.

- Current trauma, open wound on or about the treatment area

- Deformity of the target toe/toenail secondary to fungal infection/onychomycosis due to
prior injury, surgical procedures or another medical condition

- Pregnant or planning pregnancy prior to the end of study participation

- Serious mental health illness such as dementia or schizophrenia; psychiatric
hospitalization in the past two years

- Developmental disability or cognitive impairment that would preclude adequate
comprehension of the informed consent form and/or ability to follow study subject
requirements and/or record the necessary study measurements

- Involvement in litigation and/or receiving disability benefits related in any way to
the parameters of the study

- Participation in a clinical study or other type of research in the past 30 days.