Abstract:
Improvements in devices, systems and methods for non-invasively lowering intra-ocular pressure (IOP). In examples, the device applies non-invasive, focal, mechanical oscillation to the limbal region at a low amplitude and frequency, targeting the trabecular meshwork to restore outflow function and lower IOP.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefits of priority under 35 U.S.C. §119 and 120 to U.S. Provisional Application No. 61/927,615 filed on Jan. 15, 2014, and U.S. Provisional Application No. 62/018,770 filed on Jun. 30, 2014, the entireties of each being incorporated herein by reference. This application is related to U.S. patent application Ser. No. 12/995,175, filed Nov. 29, 2010, and Ser. No. 14/664,489, filed Aug. 22, 2014. 
     
    
     BACKGROUND 
       [0002]    Glaucoma, a disease characterized by intra-ocular pressure (IOP) that is too high for the preservation of a healthy optic nerve, leads to visual field loss and blindness when left untreated. Primary open angle glaucoma (POAG), the most common form of glaucoma, effects approximately 50 million people worldwide and is the leading cause of irreversible blindness. Intra-ocular pressure is currently the only modifiable risk factor for glaucoma. 
         [0003]    Aqueous humor drains from the eye through the conventional (trabecular meshwork) and unconventional (uveoscleral) outflow systems. In patients with ocular hypertension (OHT) or glaucoma, the conventional outflow system is dysfunctional, compromising pressure regulation and leading to elevated IOP. 
         [0004]    Topical ophthalmic IOP-lowering medications are typically the first-line therapy for glaucoma and OHT. However, patient compliance is a significant problem. Approximately half of diagnosed glaucoma patients are on more than one daily glaucoma medication and a quarter are on maximally tolerated medical therapy. Furthermore, no medications are currently clinically available that specifically target the conventional outflow system. 
         [0005]    Laser Trabeculoplasty (LT) is commonly a second-line treatment option for POAG utilized when medications fail. LT involves the application of thermal energy to the TM to decrease IOP, but the precise mechanism of action is unknown. Although effective in approximately half of patients up to 18 months, repeat treatments show diminished effect, probably due to its destructive nature on TM cells. Data show that LT increases cytokine release from the TM and monocyte infiltration into the eye, suggesting a mechanism of action involving thermal tissue damage and a subsequent inflammatory system activation. Such thermal injury with cell death and inflammation likely underlies the diminished responsiveness of LT upon repeated treatments. 
         [0006]    Invasive glaucoma surgery is a third-line treatment option, but it is not broadly favored due to its complication rate and lack of sustained efficacy. The most common glaucoma surgery is trabeculectomy, which involves the creation of a hole in the sclera to bypass the conventional outflow tract and drain aqueous humor into an outer bleb. However, approximately 50% of glaucoma surgery patients experience complications (e.g., infection, leakage, and irritation) and approximately 15% are likely to require a re-operation within three years. 
         [0007]    A relatively new group of alternative treatment options called minimally invasive glaucoma surgery (MIGS) is under investigation. While less invasive than traditional glaucoma surgery, MIGS still involves an incision, may result in permanent tissue damage, and/or has mixed efficacy results. For example, trabecular micro-bypass stenting, which involves placing a micro-stent in the TM during cataract surgery, has been demonstrated to be independently less effective than cataract surgery alone. 
         [0008]    Ultrasonic devices are being developed to apply focused ultrasound waves to the TM or ciliary body. Focused ultrasound is destructive in soft human tissue, and causes thermal and mechanical damage to ocular tissue. In both TM and ciliary body applications, target tissue is permanently damaged, such that repeat treatments are likely to be less effective, just like repeat LT treatments are less effective. In addition, safety is a concern given the potential for collateral tissue damage to critical ocular tissues (e.g., cornea). Acceptable long term safety and efficacy has yet to shown. 
         [0009]    Thus, there is a need for, among other things, an effective, non-invasive, atraumatic and repeatable treatment option for glaucoma and OHT patients with elevated IOP that are unable to comply with their medication regimen or on maximally tolerated medication. 
       SUMMARY 
       [0010]    According to certain aspects of the present disclosure, methods of treating an eye comprise applying focal sonic oscillation to a plurality of locations on an ocular surface of the eye using a device having a treatment head, wherein each of the plurality of locations is on a limbal region of the eye, the limbal region being spaced apart from a cornea of the eye, and wherein the focal sonic oscillation applied to each of the plurality of locations includes an oscillation frequency and duration. 
         [0011]    In some embodiments, methods of treating an eye may include one or more of the following: the plurality of locations may be disposed in a circular pattern about the cornea; the plurality of locations may include at least a first location and a second location, and a duration of the focal sonic oscillation applied to the first location may be at least partially concurrent with a duration of the focal sonic oscillation applied to the second location; the plurality of locations may include at least a first location and a second location, and the first location may be positioned 180 degrees from the second location; the plurality of locations may include at least a first location and a second location, and the first location may be spaced from the second location by less than 180 degrees; the circular pattern may be facilitated by a template to guide the treatment head; the focal oscillation may be applied by one or more pins in the treatment head; the one or more pins may be driven by one of a motor and a magnetic solenoid; the one or more pins may be driven hydraulically or pneumatically; the focal oscillation may be applied by a pulsating fluid ejected out of the treatment head; the focal oscillation may be activated when a measured pressure is within a range having a lower limit indicative of the treatment head being applied to and in contact with a surface of the eye and an upper limit corresponding to a maximum pressure threshold; the measured pressure may be measured by a sensor disposed within the treatment head; the sensor may be a load cell; each of the one or more pins may be configured to oscillate between a first position and a second position, wherein, when in the first position, the one or more pins may be withdrawn into the treatment head, and, when in the second position, a distal portion of the one or more pins may be extended out of the treatment head; the focal oscillation may be applied to the limbal region of the eye without increasing a temperature of eye tissue; the focal oscillation may be applied to the limbal region of the eye by repeatedly pressing the limbal region with a distal end of an oscillating pin; the treatment head may include a portion configured to be positioned on and in contact with a limbus of the eye; the portion may include an edge configured to complement the limbus; and the treatment head may include a distal-most surface angled relative to a longitudinal axis of the treatment head, wherein the distal-most surface may include an opening through which a distal portion of an oscillating element may extend out of the treatment head and withdraw into the treatment head. 
         [0012]    According to certain additional aspects of the present disclosure, methods of treating an eye comprise positioning a pin of a treatment device at a first location on an ocular surface of the eye, wherein the first location is spaced from the cornea; and oscillating the pin to repeatedly apply a force to the first location, wherein the force is applied at a frequency outside of the ultrasonic range. 
         [0013]    In some embodiments, methods of treating an eye may include one or more of the following: the treatment device may include a distal surface with an edge corresponding to a shape of the eye; the treatment device may include a nosecone configured to receive an entirety of the pin therein, and a distal surface of the nosecone may include an opening through which a distal end of portion of the pin may be configured to protrude out of the nosecone; the distal surface of the nosecone may be angled relative to an oscillating axis of the pin; the nosecone may be formed of a material that allows visualization of the pin through the nosecone; the force applied to the first location may not increase a temperature of eye tissue; the nosecone may be selectively removable from the treatment device; the pin may not pierce tissue; and the first location on the ocular surface may be at the limbus, and the force applied to the first location may be transmitted to ocular structures spaced from an exterior surface of the eye. In some embodiments, methods of treating an eye may further comprise positioning the pin at a second location on the ocular surface of the eye, wherein the second location may be spaced from the cornea; and oscillating the pin to repeatedly apply a force to the second location. In some embodiments, the first and second locations may be spaced by 180 degrees. 
         [0014]    Additional characteristics, features, and advantages of the described embodiments will be set forth in part in the description that follows, and in part will be apparent from the description, or, may be learned by practicing the disclosure. The disclosed subject matter can be realized and attained by way of the elements and combinations particularly pointed out in the appended claims. 
         [0015]    It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only, and are not restrictive of the described embodiments, as claimed. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    The drawings illustrate example embodiments of the present disclosure. The drawings are not necessarily to scale, may include similar elements that are numbered the same, and may include dimensions and angles by way of example, not necessarily limitation. In the drawings: 
           [0017]      FIG. 1  is a plan view of a system according to an embodiment of the present disclosure including a control box, power source, optional foot switch and handset; 
           [0018]      FIG. 2  is a perspective view of the handset shown in  FIG. 1 ; 
           [0019]      FIG. 3  is an exploded view of the handset shown in  FIG. 2 ; 
           [0020]      FIGS. 4A-4D  are perspective, end, top and side views of a nosecone on the handset shown in  FIG. 3 ; 
           [0021]      FIGS. 4E-4G  are perspective views of alternative nosecone embodiments; 
           [0022]      FIG. 5  is an anatomical illustration of the handset in use with the nosecone applied to the ocular surface; 
           [0023]      FIG. 6A  is a longitudinal sectional view of the distal assembly of the handset; 
           [0024]      FIG. 6B  is a longitudinal sectional view of an alternative (removable and disposable) distal assembly of the handset; 
           [0025]      FIG. 7  is a perspective view of a template for use with the handset; 
           [0026]      FIG. 8  is a schematic view of an alternative drive mechanism; 
           [0027]      FIG. 9  is a perspective view of another alternative handset; 
           [0028]      FIG. 9A  is a sectional view taken along line A-A in  FIG. 9 ; 
           [0029]      FIG. 10  is a perspective view of yet another alternative handset; 
           [0030]      FIG. 10A  is a sectional view taken along line A-A in  FIG. 10 ; 
           [0031]      FIG. 10B  is a top view of the rotating ring shown in  FIG. 10A ; 
           [0032]      FIG. 11  is a perspective view of a further alternative handset; 
           [0033]      FIG. 11A  is a sectional view taken along line A-A in  FIG. 11 ; and 
           [0034]      FIG. 11B  is a top view of the rotating ring shown in  FIG. 11A . 
       
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0035]    Features of each and any embodiment disclosed herein may be combined with any other embodiment disclosed herein. 
         [0036]    With reference to  FIG. 1 , a Deep Wave Trabeculoplasty (DWT) system  10  may include a control box  20 , a power supply  30 , an optional foot pedal switch  40 , and a handset  100 . As will be described in more detail hereinafter, the handset  100  may contain an electrically powered motor, a linearly oscillating probe with a distal tip, and a positioning guide. The motor may be connected to the probe via a mechanical coupler that moves the probe axially at a selected frequency (e.g., 10-500 Hz) and amplitude (e.g., 0.5-1 mm). The frequency selected for application to the patient&#39;s eye may be within a range of frequencies (e.g., sonic or sub-ultrasonic) that does not generate heat, increase the temperature of eye tissue, or otherwise damage eye tissue. The distal tip may extend beyond the positioning guide on the downward stroke, and may be set back inside the positioning guide on the upward stroke. The positioning guide may be configured to rest on the surface of the eye and conform to the limbal region such that the distal tip contacts the surface of the eye. The positioning guide thus controls the amplitude of tissue deflection while the probe tip applies mechanical oscillation proximate the limbus on the surface of the eye. 
         [0037]    The mechanical oscillation may be transmitted to the trabecular meshwork (TM), which lies immediately posterior to the limbal region in the anterior chamber of the eye. Normal functioning TM responds to stretch to regulate the outflow of aqueous humor and control IOP. Mechanical oscillation by the DWT system  10  is believed to stretch the TM during treatment, initiating a physiological cascade to restore function of the TM and increase the outflow of aqueous humor, thereby decreasing IOP. 
         [0038]    From the published literature, it appears that technology that causes or mimics ATP release from TM cells would be an effective therapy for glaucoma. In line with this idea, DWT therapy involves the application of mechanical vibration on the surface of the eye proximal to the limbus using the DWT system  10 . The DWT system  10  causes scleral deflection (0.5-1 mm tissue displacement) on its downward stroke. Since the conventional outflow tissues reside immediately below the limbus surface, they are likely stretched upon each cycle of the distal tip. In healthy eyes, stretching of the TM by the DWT system  10  likely leads to release of ATP and activation of several signaling cascades that result in increased outflow facility and lower IOP. In glaucomatous eyes, it is likely that direct application of mechanical stress to a tissue that has become insensitive to mechanical stimuli due to disease processes and/or tissue sclerosis may activate signaling pathways that have been dormant, thus restoring outflow facility. 
         [0039]    With continued reference to  FIG. 1 , the control box  20  may include a housing  22 , a push-button switch  24 , an indicator light  26  and several plug receptacles  28  configured to receive electrical connections from the other components  30 ,  40 ,  100 . Power supply  30  (e.g., AC adapter) may provide electrical power to the control box  20  and handset  100 . The foot pedal switch  40  may optionally be plugged into the control box  20 , such that the foot pedal switch  40  serves as an alternative to push-button switch  24 . 
         [0040]    The housing  22  of the control box  20  may contain electronic control circuitry (not shown), which may provide power and control signals to the motor in the handset  100 . The electronic control circuitry may include a timer such that depressing switch  24  (or foot pedal switch  40 ) activates the motor in the handset  100  for a predetermined period of time (e.g., 10 seconds) or for as long as the switch is depressed. The indicator light  26  may be illuminated when the motor in the handset  100  is activated. The control circuitry may drive the motor at a fixed or variable frequency. For example, the control circuitry may measure the load on the motor and compensate power to hold the frequency at a fixed value. 
         [0041]    Although described as discrete components, the functionality of the control box  20  and/or power supply  30  may be incorporated into the handset  100 . For example, the handset  100  may include rechargeable batteries, control circuitry, an indicator light and an activation switch. In this configuration, the handset  100  may be cordless and reside in a recharging unit when not in use. 
         [0042]    With reference to  FIG. 2 , the handset  100  is shown in more detail. Handset  100  may include a case  102  configured in the shape of an “L”, with the long segment held in the anterior (palmar) side of the hand like a pen and the short segment resting on the posterior (dorsal) side of the hand. As will be described in more detail hereinafter, a motor may be contained in the short segment of the case  102  such that the weight of the motor is carried by the wrist and the long segment of the case  102  may be easily manipulated by the fingers for better control of the tip as it is applied to the ocular surface. 
         [0043]    A cord  108  may be connected to the short segment of the case for connection to the control box  20 . A strain relief  109  may be placed over the cord  108  and connected to the case  102  to prevent damage to the cord  108  at the junction to the case  102 . The cord  108  may be electrically connected to the motor in the case as will be described in more detail hereinafter. 
         [0044]    A screw-on collar  104  may be connected to the distal end of the case  102  and a snap-on nosecone  110  may be connected to the distal end of the collar  104 . An oscillating pin  106  (e.g., 1.0 mm diameter) defining an atraumatic distal tip may reside in a channel in the collar  104  and nosecone  110 . In some embodiments, the distal tip of pin  106  may include a semispherical configuration such that the tip does not pierce eye tissue when placed in contact with eye tissue. Oscillating pin  106  may oscillate between a first refracted position (see, e.g.,  FIG. 5 ) and a second extended position (see, e.g.,  FIG. 2 ). In the first retracted position, a distal end portion of oscillating pin  106  may be completed withdrawn into and received by nosecone  110 . That is, in some embodiments, a distal-most tip of oscillating pin  106  may not protrude past a distal periphery of, e.g., distal surface  114  (shown in  FIG. 4A , e.g.) when the pin  106  is in the first retracted position. When the pin is in the second extended position, the distal-most tip of the pin  106  may protrude beyond the distal periphery of distal surface  114 . Further, the collar  104 , nosecone  110  and oscillating pin  106  may be removable from the case  102  for purposes of cleaning or replacement between uses, while the remainder of the handset  100  may be reusable. 
         [0045]    As will be described in more detail hereinafter, the nosecone  110  may include an anatomically conforming distal surface. The nosecone  110  may be formed of transparent or semi-transparent material for visualization of the pin  106  when applied to the ocular surface. The nosecone  110  may be rotatable relative to the collar  104  and case  102  to orient the distal surface thereof relative to the ocular surface without the need to rotate the entire handset  100 . These features may serve to ensure proper placement of the tip of the oscillating pin  106  on the limbus and limit scleral deflection. 
         [0046]    With reference to  FIG. 3 , the internal components of the handset  100  may be shown and described. As mentioned previously, the handset  100  includes a motor  120  that oscillates the pin  106  at a desired frequency defined by control signals from the control box  20 . Motor  120  may be mechanically coupled to the pin  106  via a cam  122  and link truss  124 . Whereas the oscillation frequency (e.g., sonic) of the pin  106  may be defined by the control signals sent to the motor  120  from the control box  20 , the cam  122  may be used to define the oscillating amplitude (e.g., 0.5-1.0 mm) of the pin  106 . The motor  120  may be mounted to the case  102  using suitable mounting hardware  126  (e.g., O-ring, L-bracket and screws). The cam  122  may be connected to the shaft of the motor  120  using conventional set screws, and the link truss  124  may be connected to the off-set shaft of the cam  122  using conventional bearing and retaining ring hardware  128 . The oscillating pin  106  may be fixed to and extend from the distal end of the link truss  124 . A threaded bearing  130  may be fixed to the case  102  by a fastener, such as, e.g., pin  132 . The collar  104  may be screwed onto the threaded bearing  130 , and an O-ring  134  may provide a fluid barrier to prevent the ingress of liquid through the channel containing the oscillating pin  106 . Thus, as the motor  120  rotates cam  122 , the link truss  124  moves pin  106  linearly through threaded bearing  130 , collar  104  and nosecone  110 . 
         [0047]    A load cell (not shown) may be incorporated into the handset  100  and coupled to any of the nosecone  110  embodiments disclosed herein. The load cell may measure pressure applied to the nosecone  110  when the same is applied to the ocular surface. Electronics resident in the control box  20  or the handset  100  may be connected to the load cell. The electronics may activate the motor  120  automatically when the pressure is in a specified range. A lower limit of the range may indicate the nosecone  110  is being applied to the ocular surface with sufficient pressure, and an upper limit of the range may indicate too much pressure is being applied to the ocular surface. 
         [0048]    With reference to  FIGS. 4A-4D , the nosecone  110  is shown in more detail. Dimensions are provided by way of example, not necessarily limitation, and are given in inches with millimeter equivalents shown in boxes. For example, with reference to  FIGS. 4B-4D , dimension “A” may include a radius of about 7 mm, dimension “B” may include a distance of about 10 mm, dimension “C” may include a distance of about 4.0 mm, dimension “D” may include a distance of about 0.75 mm, dimension “E” may include a distance of about 7.1 mm, dimension “F” may include a distance of about 2.4 mm, dimension “G” may include a distance of about 3.0 mm, dimension “H” may include an angle of about 30 degrees, dimension “I” may include a distance of about 17.9 mm, and dimension “J” may include a distance of about 18.2 mm. The term “about” means to be nearly the same (or the same) as a referenced dimension. As used herein, the term “about” generally should be understood to encompass ±5% of a specific dimension. 
         [0049]    Nosecone  110  may include a thru hole or channel  112  in which resides the oscillating pin  106 . Nosecone  110  may also include a distal body portion  115  having a distal surface  114  configured to contact the limbus and sclera around the cornea. Distal surface  114  may be planar or concave with an inside contour approximating the spherical shape of the eye. Distal surface  114  may be formed at an angle (e.g., 30-60 degrees) relative to the oscillating axis of the pin  106  such that the handset  100  may be held comfortably at an angle when the nosecone  110  is applied to the ocular surface. Distal surface  114  provides a large surface area relative to pin  106  to rest on the sclera without substantial pressure, and allows the pin  106  to apply focal pressure on the limbus. Nosecone  110  may include a cutout portion  116  defining an arc  118  which may have a radius that is slightly greater than the radius of the cornea. For example, the adult cornea is typically elliptical and may have a horizontal diameter of 11.5-12.6 mm (radius of 5.75-6.3 mm) and a vertical diameter of 10.5-11.7 mm (radius of 5.25-5.85 mm). Pediatric corneas may have a diameter of 9-10 mm (radius of 4.5-5.0 mm). Thus, the radius of the arc  118  may be selected to be in the range of 4.5 mm to 7 mm, for example. Different sized nosecones  110  may be provided to accommodate the appropriate size selection of the arc  118 . Cutout portion  116  and arc  118  allow the oscillating pin  106  to be positioned on the limbus without contacting the cornea. The hole  112  may have a diameter that is slightly larger than the oscillating pin diameter (e.g., 1.0 mm) and may be positioned immediately adjacent the arc  118 , defining a narrow gap between the hole  112  and the arc (e.g., 0.25-1.0 mm or more preferably 0.75 mm (dimension “D” in  FIG. 4B ) allowing the pin  106  to be positioned immediately adjacent the cornea on the limbus. Forming the nosecone  110  of semi-transparent or transparent material allows visualization of the oscillating pin  106  and aids in precise positioning of the pin  106  on the limbus. 
         [0050]    With reference to  FIGS. 4E-4G , alternative nosecone embodiments are shown in perspective view. In  FIG. 4E , the distal facing surface  114 A of the nosecone  110 A may be concave with a radius of curvature of about 12.5 mm to conform to the ocular surface where the globe of the eye has a diameter of about 25 mm (radius of about 12.5 mm). In  FIG. 4F , material may be removed from the distal body portion  115 B to provide for improved visualization of the pin  106  thru the transparent material of the nosecone  110 B while maintaining roughly the same area of the distal facing surface  114 B for contact with the ocular surface. In  FIG. 4G , additional material may be removed from the distal body portion  115 C to provide for improved visualization of the pin  106  thru the transparent material of the nosecone  110 C while reducing the area of the distal facing surface  114 C for contact with the ocular surface. 
         [0051]    With reference to  FIG. 5 , the position of the oscillating pin  106  relative to ocular anatomy may be better appreciated. The trabecular meshwork lies deep to the limbal region  206  defined by the transition from the cornea  202  to the sclera  204 . The distal surface  114  of the nosecone  110  may be placed on the sclera  204  such that arc  118  defined by the cutout  116  is immediately adjacent the corneal edge. This position places the oscillating tip  106  on the limbus  206  to transmit focal mechanical oscillation to the trabecular meshwork. 
         [0052]    With reference back to  FIGS. 1 and 2 , and continued reference to  FIG. 5 , clinical use of the DWT system  10  may be appreciated by the following description, given by way of example, not limitation. To prepare the DWT system for use, the tip assembly may be replaced or removed for cleaning. The nosecone  110  may be un-snapped from the collar  104  or the nosecone  110  and collar  104  assembly may be unscrewed from the threaded bearing  134 . The tip assembly may be washed in soapy water and rinsed. The tip assembly (or a new one) may be replaced onto the handset  100  and all surfaces of the handset  100  may be wiped with alcohol. The handset  100  cable  108  may then be connected to the designated receptacle  28  in the control box  20 . The power supply  30  may then be connected to the control box and plugged into a wall outlet. The system  10  may then be tested by depressing the button  24  on the control box  20 . The tip  106  oscillates for a preset period of time (e.g., 10 sec.). 
         [0053]    Then, with the subject supine, a lid speculum is placed on the first eye to keep the eyelids open. One drop of a suitable anesthetic, such as, e.g., proparacaine, is placed over the central cornea and repeated after 30 seconds. Lidocaine gel is then placed over the entire cornea as well as around the limbus for 360 degrees. Therapy is initiated by placing the nosecone  110  on the sclera and aligning the curved edge  118  over the limbal vessels. Gentle pressure should be used until the conjunctiva is slightly indented on either side of the nosecone  110 . This pressure is preferably held constant throughout the duration of treatment. While maintaining position and pressure of the nosecone  110  as indicated, the ON button  24  on the control box  20  is then depressed, causing the tip  106  to oscillate for a specific period of time. Each quadrant of the limbus may receive 4-6 non-overlapping 10-20 second spot treatments for example, with a total of 16-36 applications around 360 degrees of the limbus. In some embodiments, therapy may be applied as deemed appropriate by a practitioner. For example, a first spot treatment may be applied at a first location and a second spot treatment may be applied at a second location that is 180 degrees (or diametrically opposed) away from the first location. In other embodiments, the second location may be adjacent (e.g., less than 180 degrees away) from the second location. Additional anesthetic (lidocaine gel) can be used to maintain patient comfort. Once the treatment is completed, the speculum is removed. The opposite eye is then treated using the identical procedure outlined above. Suitable non-inflammatory and/or pain reducing medication may be then administered to the patient. For example, in one embodiment a nonsteroidal anti-inflammatory drug such as Nevanac may be given to the subject to be used one drop four times per day in both eyes for four days. 
         [0054]    To aid with uniform coverage, it may be desirable to mark quadrants around the limbus with a blue pen, with 4 spots 90 degrees apart from each other, for example. A ring-shaped template may be applied to the ocular surface around the treatment area for additional positioning guidance. Also, it is helpful to visualize the oscillating tip  106  thru the semi-transparent nosecone  110  to align the force vector from the tip  106  with the trabecular meshwork, which is a relatively small target (0.3 mm long). Further, it is helpful to use slight indentation of conjunctiva as indicator of correct pressure. The patient should feel vibrations throughout the treatment. Because it tip oscillation amplitude may be small (e.g., 0.5-1.0 mm), and because the oscillating tip  106  may push back, it is helpful to hold the handset  100  with steady pressure and position for the entirety of each spot treatment. 
         [0055]    With reference to  FIG. 6A , a longitudinal sectional view of the distal assembly of the handset  100  is shown. This assembly reflects the configuration shown in  FIG. 3  where the oscillating pin  106  is fixed to the link truss  124  and extends through the threaded bearing  130 , which in turn is fixed to the case  102  by pin  132 . The collar  104  is releasably screwed onto the threaded bearing  130  with O-ring  134  providing a seal, and the nosecone  110  is releasably snapped onto the collar  104 . Thus, with this arrangement, the collar  104  and nosecone  110  may be detached from the remainder of the handset, but the pin  106  remains fixed in place. This allows for replacement of the nosecone  110  and/or collar  104  and cleaning of the pin  106 . 
         [0056]    An alternative configuration is shown in  FIG. 6B , which allows for replacement of all components that may come into contact with ocular tissues, including nosecone  110  and pin  106 . In this embodiment, the pin  106  includes a proximal portion  106 A and a distal portion  106 B, with the proximal end of the proximal pin portion  106 A fixed to the link truss  124  as before. The distal end of the proximal pin portion  106 A includes an a head  107 A that abuts but is not fixed to a corresponding head  107 B on the proximal end of the distal pin portion  106 B. A spring  105  may be disposed about the distal pin portion  106 B to bias the distal pin portion  106 B in the retracted position. With this arrangement, the proximal pin portion  106 A is not fixed to the distal pin portion  106 B but nevertheless provides for oscillation of the tip of the pin  106  as in prior embodiments. Specifically, the proximal pin portion  106 A transfers push force to the distal pin portion  106 B on the down stroke, and spring  105  retracts the distal pin portion  106 B on the upstroke. This arrangement allows the distal pin portion  106 B to be detached from the handset  100  by unscrewing the collar  104  such that the collar  104 , pin  106 B and nosecone  110  may be replaced as a single-use disposable while the remainder of the handset  100  may be reused. 
         [0057]    With reference to  FIG. 7 , a template  210  for use with the handset  100  is shown in perspective view. Template  210  may include an annular ring portion  212  connected to a handle  214  by arms  216  to define openings  217  through which the eye may be visualized. A series of holes  218  may be equally spaced around the annular ring  212 . Holes  218  may be sized and configured to accommodate oscillation of the pin  106  of handset  100  while controlling the position and angle of the pin  106 . The diameter of the annular ring  212  may be sized to position the holes  118  over the limbal region on the ocular surface such that the pin  106  is directed to the underlying trabecular meshwork. Because of anatomical variation, the template  210  and more specifically the diameter of the annular ring  212  along the centerline of the holes  218  may come in different sizes, ranging from about 10 mm-20 mm, for example. Additionally, the inside diameter of the annular ring  212  may be selected to avoid contact with the cornea, and may be round or oval depending on the shape of the cornea. 
         [0058]    Template  210  is configured to be placed on the ocular surface around the limbal region and aid in positioning the pin  106  at uniformly spaced-apart spot treatments around the underlying trabecular meshwork. To accommodate the thickness of the annular ring  218  and maintain the desired excursion (e.g., 1 mm) of the pin  106 , the pin  106  may be extended and/or the nosecone  110  may be replaced with a shorter-length interface to engage the template  210 . Template  210  may be formed of a transparent material to allow visualization of the pin  106  engaging the ocular surface. Additionally, the tissue-contacting surface of the annular ring  212  may be formed of or include a soft atraumatic material (e.g., silicone) to reduce the likelihood of injury to the ocular surface. 
         [0059]    With reference to  FIG. 8  an alternative drive mechanism  230  contained in housing  240  is shown schematically. The associated components including electrical connections and control system are not shown, but the same design principles may be applied consistent with the teachings with reference to  FIG. 1  and system  10 . In this embodiment, the drive mechanism  230  is used to actuate multiple pins  236  in an alternating manner. This arrangement allows for multiple spot treatments at the same time, thus reducing the procedure time. As shown, the drive mechanism  230  includes a motor  232  that rotates shaft  234  and two cams  238  offset by 180 degrees. The cams  238  displace drive cylinders  252  on the downward stroke. Springs  253  are disposed about pins  236  in the housing  240  to bias each cylinder  252  on the upward stroke. Thus, the pins  236  are driven in a linearly oscillatory fashion, causing excursion of the pins  236  from the positioning guides  244 . The positioning guides  244  may be anatomically configured in a similar fashion to nosecone  110  to e.g., avoid cornea  202 . 
         [0060]    With reference to  FIG. 9 , an alternative handset  260  in shown schematically in perspective view. Handset  260  includes a handle  262  and a magnetically driven treatment head  264  in the shape of a ring defining a through hole  266 . A control cable  268  is connected to the handle  262  and is operably connected to the treatment head  264  via wires  270 . As best seen in  FIG. 9A , which is a sectional view taken along line A-A in  FIG. 9 , the treatment head  264  includes a fixed base  272  connected to the handle  262  and a detachable portion  274  connected to the fixed base  272  by threads  276 . Both the fixed base  272  and the detachable portion  274  are in the shape of an annular ring, with the fixed base  272  defining an L-shaped cross-section that is configured to releasably receive the detachable portion  274  via threads  276 . 
         [0061]    With continued reference to  FIG. 9A , the detachable portion  274  is hollow and contains a magnetic ring  278  with an array of pins  280  projecting therefrom. The array of pins  280  is aligned with corresponding holes  282 . The magnetic ring  278  is sized and shaped relative to the hollow portion of the detachable portion  274  such that the magnetic ring  278  may be displaced longitudinally causing the pins  280  to extend out of or retract into the corresponding holes  282 . Such displacement may be achieved using magnetic forces created by driver coil  284  applied to the magnetic ring  278 . For example, the driver coil  284  may be powered by an alternating electrical signal to drive the magnetic ring  278  in alternating posterior and anterior directions, causing the pins to oscillate in a longitudinal (anterior-posterior) direction at a frequency corresponding to the frequency of the alternating electrical signal. With the treatment head  264  placed on the ocular surface, the through hole  266  centered around the cornea such that cornea is not contacted, and the holes  282  aligned with the limbal region, the pins  282  may apply mechanical oscillating forces to the underlying trabecular meshwork simultaneously. The size, number and arrangement of the pin array  280  and corresponding holes  282  may vary. In addition, the magnetic ring  278  may be a continuous ring with uniform polarity such that all pins  280  are advanced and retracted in unison, or the magnetic ring  278  may be divided into discrete arc sections with alternating polarity such that pins  280  corresponding to adjacent arc sections are alternately advanced and retracted. 
         [0062]    With reference to  FIG. 10 , another alternative handset  300  in shown schematically in perspective view. Handset  300  includes a handle  302  and a fluid driven treatment head  304  in the shape of a ring defining a through hole  306 . A fluid line  308  is connected to the handle  302  and is operably connected to the treatment head  304  via lumen  310 . As best seen in  FIGS. 10A and 10B , the treatment head  304  includes a rotating ring  312  and an array of spring loaded pins  314  disposed in a hollow ring housing  316 . The rotating ring  312  includes spaced-apart turbine blades  318  and one or more spaced-apart cams  320  that engage the base of the pins  314 . The hollow ring housing  316  includes a series of holes  322  aligned with and corresponding to the pins  314 . 
         [0063]    With continued reference to  FIGS. 10A and 10B , the rotating ring  312  may be driven by pressurized fluid (liquid or gas) via pressure line  308  and lumen  310  causing rotation of the ring  312  as the fluid engages the turbine blades  318  and eventually exits exhaust port  324 . As the ring  312  rotates, the cam (or cams)  320  sequentially engages the base of each spring-loaded pin  314 , causing displacement of the pin  314  such that it extends through the corresponding hole  322  of the housing. As ring  312  continues to rotate and the cam  320  passes each pin  314 , the associated spring causes the pin  314  to retract back into the housing  316 . With this arrangement, the pins  314  sequentially oscillate longitudinal (anterior-posterior) direction at a frequency corresponding to the pressure-controlled rotational velocity or ring  312  and the number of cams  320 . With the treatment head  304  placed on the ocular surface, the through hole  306  centered around the cornea and without contacting the cornea, and the holes  322  aligned with the limbal region, the pins  314  may apply mechanical oscillating forces to the underlying trabecular meshwork sequentially around the circumference. The size, number and arrangement of the pin array  314  and corresponding holes  322  may vary. In addition, number and spacing of the cams  320  may vary to provide the desired number, timing and circumferential position of pins  314  actuated. 
         [0064]    With reference to  FIG. 11 , yet another alternative handset  340  in shown schematically in perspective view. Handset  340  includes a handle  342  and a fluid driven treatment head  344  in the shape of a ring defining a through hole  346 . A fluid line  348  is connected to the handle  342  and is operably connected to the treatment head  344  via lumen  350 . As best seen in  FIGS. 11A and 11B , the treatment head  344  includes a rotating ring  352  including spaced-apart turbine blades  358  and one or more spaced-apart exhaust ports  360 . The rotating ring  352  is disposed in a hollow ring housing  356  that includes a series of holes  362 . 
         [0065]    With continued reference to  FIGS. 11A and 11B , the rotating ring  352  may be driven by pressurized fluid (liquid or gas) via pressure line  348  and lumen  350  causing rotation of the ring  352  as the fluid engages the turbine blades  358  and eventually exits exhaust port  360  when aligned with one of the holes  362 . As the ring  352  rotates, the exhaust port (or ports)  360  sequentially aligns with each hole  362  in the housing  356 . The fluid then exits the hole  362 , acting as a fluid equivalent of the pins described in other embodiments. With this arrangement, fluid pulses sequentially exit in a longitudinal (posterior) direction at a frequency corresponding to the pressure-controlled rotational velocity or ring  352  and the number of exhaust ports  360 . With the treatment head  344  placed on the ocular surface, the through hole  346  centered around the cornea such that treatment head  344  does not contact the cornea, and the holes  362  aligned with the limbal region, the exhaust fluid may apply mechanical oscillating forces to the underlying trabecular meshwork sequentially around the circumference. The size, number and arrangement of the holes  362  may vary. In addition, number and spacing of the exhaust ports  360  may vary to provide the desired number, timing and circumferential position of fluid pulses. 
         [0066]    In any of the foregoing embodiments, irrigation may be supplied to the treatment head to lubricate the spot treatment area. Suitable liquids include balanced salt solutions and other topical irrigation fluids. In addition or in the alternative, the treatment head may include a seal ring (e.g. silicone) about its distal-facing perimeter to provide a cushion and/or seal against the ocular surface. In addition or in the alternative, the treatment head may incorporate a vacuum to stabilize the device against the ocular surface. 
         [0067]    The foregoing discussion of the invention has been presented for purposes of illustration and description. The foregoing is not intended to limit the invention to the form or forms disclosed herein. Although the description of the invention has included description of one or more embodiments and certain variations and modifications, other variations and modifications are within the scope of the invention, e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure. It is intended to obtain rights which include alternative embodiments to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges or steps are disclosed herein, and without intending to publicly dedicate any patentable subject matter.