The Strabismus Research Foundation (SRF) is a 501(c)(3) non-profit operating foundation dedicated to translational research in ocular motility.

Staff

ABS
Alan B Scott, MD

Director and Senior Scientist at The Strabismus Research Foundation (SRF; 2016-).
Senior Scientist at Eidactics (2016-).
Senior Scientist at The Smith-Kettlewell Eye Research Institute (SKERI; 1959-2016).
JMM
Joel M Miller, PhD

Director of Research at SRF (2016-).
Director & Senior Scientist at Eidactics (1993-).
Senior Scientist at SKERI (1982-2013).
TCN
Talita Cunha Namgalies MD

Clinical Scientist (2018-).
Ophthalmologist, Brazilian Air Force, IOBH & Guimaraes Hospital (2015-2017).

Collaborators

TDM
Taliva D Martin, MD

Pediatric ophthalmologist at California Pacific Medical Center.
ID
Iara Debert, MD, PhD

Research Fellow at Eidactics (2014-2015).
Clinical Fellow at SRF (2014-2015).
Attending Ophthalmologist at Hospital das Clinicas, Univ of São Paulo (2012-present).

Presentations & Classes

  • Cunha TM, Miller JM, Scott AB (2018). Injection of Bupivacaine and Botulinum Type A Toxin to Treat Strabismus. AAPOS Meeting (PDF).
  • Cunha TM, Miller JM, Scott AB (2018). Injections to Treat Strabismus. Jampolsky Fellows Meeting (PDF).
  • Miller JM (2017). SRF Board of Directors Meeting, 2017.07.13. SRF (KeynotePowerpointPDF).
  • Akhtar N (2017). Insulin-like Growth Factor-1 (IGF-1) and muscle hypertrophy. SRF (PDF).
  • Miller JM (2017)Explanatory & pragmatic research. Eidactics (PDF).
  • Miller JM (2017). Non-inferiority testing. Eidactics (PDF).
  • Miller JM (2016)The Orbit™ Gaze Mechanics Simulation. Eidactics (PDF).
  • Miller JM, Debert I (2016)History of Botulinum Toxin Therapy. SRF (PDF).
  • Miller JM, Scott AB, Debert I (2016)Bupivacaine Injection Treatment Of Strabismus. SRF (PDF
Projects

Pharmacologic Treatment of Strabismus

Strabismus
, misalignment of the eyes, is mostly treated surgically by compensatory impairment of healthy muscles, rather than by correcting the underlying disorder. Incisional surgery is costly, results in scarring that makes
 frequently-needed followup surgery difficult, and requires general anesthesia that may be problematic in some populations (smarttots.org). We have long been interested in pharmacologic injection treatments to supplement or replace conventional surgery:
  • Debert I, Miller JM (2015)Injection Treatment of Strabismus. Eidactics (PDF).
Oculinum® (now called Botox®) was originally developed to relax and lengthen "tight" eye muscles (Scott 1980). It was the first successful pharmacologic injection treatment for strabismus, and the first therapeutic application of botulinum toxin. So dauntingly counterintuitive was the notion of injecting this most toxic substance, without visual guidance, alongside the healthy eye of an alert patient, that its safe and efficacious development, and the many and varied applications that followed, make a uniquely fascinating story of medical discovery:
  • Debert I, Miller JM (2015)History of Botulinum Toxin Therapy. Eidactics (PDFOn Wikipedia).
We’ve now turned our attention to the problem of strengthening and shortening "weak" muscles.
 Bupivacaine (BUP) is a selective myotoxin with effects analogous to mechanical overloading – myofiber damage followed by hypertrophy – and we have been developing BUP injection as a practical method for correcting eye misalignmentsBupivacaine dissociates sarcomeres (the muscle's contractile elements), triggering satellite cells (a kind of stem cell) to rebuild the damaged fibers, stronger, stiffer, and at reduced length. Almost 200 volunteer strabismus patients have received BUP injection treatments, most also with botulinum toxin in the antagonist muscle to prevent stretching while the BUP-injected muscle rebuilds. Here's what you need to know:
  • Miller JM, Scott AB, Danh KK, Strasser D, Sane M (2013). Bupivacaine injection remodels extraocular muscles & corrects comitant strabismus. Ophthalmology, vol 120, num 12, December (Authors' Cut PDFPublisher's site).
  • Debert I, Miller JM, Danh KK, Scott AB (2016). Pharmacologic Injection Treatment of Comitant Strabismus. Journal of AAPOS, vol 20, pgs 106-111. (Authors' Cut PDFPublisher's site).
  • Cunha TM, Miller JM, Scott AB (2018) Injection of Bupivacaine & Botulinum Type A Toxin to Treat Strabismus. Transactions of ISA. (Manuscript PDF)
Injection treatment for horizontal strabismus achieves stable corrections lasting up to 10 yrs (each curve in the graph shows alignment data for a cohort of patients who all returned for the same followup measurements). Dosage guidelines are shown in the table.

Having demonstrated the clinical effectiveness of BUP treatment in comitant adult strabismus, we are now developing injection techniques suitable for children. 
BUP injection may also have clinical applications in other small muscles.
Accurate Injection of Eye Muscles in Children (Knights Templar Eye Foundation • Taliva D Martin, MD & Alan B Scott, MD)

Early treatment of infantile strabismus facilitates normal development of stereopsis (depth perception from binocular vision), prevents amblyopia (suppression of vision in one eye), and improves cosmesis. But surgical correction in young children is problematic: [1] frequently necessary follow-up surgery is made more difficult by scarring from the initial surgery; it would be better if non-surgical treatment were used, at least initially, and [2] strabismus surgery requires prolonged general anesthesia, which may cause cognitive deficits in a developing brain (eg, Rappaport et al 2015). 

SRF STIM-EMG, KTEF Presentation
Botulinum toxin A (BTXA) injection treatment of Extraocular muscles (EOMs) is an effective and widely-accepted alternative to conventional surgical treatment of esotropia. Because EOMs lie deep in the orbit, a technique is needed to accurately place the injection needle within the target muscle. In awake, cooperative adults, electromyography (EMG) signals are recorded from the tip of the injection needle, which is advanced until the relationship of the EMG signal to the patient’s voluntary eye movement indicates desired placement. But most strabismus patients are children, who must be briefly anesthetized to accept injection treatment, and anesthetized muscles show little or no movement-related electrical activity. Injection treatment in children is therefore currently performed without EMG guidance, and so, cannot target the deeper neuromuscular junctions, resulting in reduced treatment efficacy and unwanted effects on neighboring muscles. Although no useful EMG signal can be recorded, an anesthetized muscle can be readily 
stimulated. We have determined from animal studies (funded by The Pacific Vision Foundation) that brief trains of 0.5-5.0 mA, 1 ms square-wave pulses at ~200 Hz produce eye movements characteristic of optimal needle placement. With the support of the Knights Templar Eye Foundation, we developed a suitable stimulating device, and have proposed to evaluate its effectiveness on young strabismus patients. Stimulation-guided injection is expected to be similarly useful in extending to children other pharmacologic injection treatments now under development.

We thank the Knights Templar Eye Foundation for supporting this clinically significant work in its early stages. In the photo, Bud Ramsey, Past Grand Commander, tours SRF's labs and presents the grant check to Drs Martin & Scott.
Activating the Levator to Elevate the Eyelid

Blepharospasm sufferers may be functionally blind despite having normal eyes because of spasms in surrounding facial muscles and eyelid apraxia, inability to raise the eyelids or keep them raised. It is a disorder of central control, possibly related to abnormal function of the basal ganglia, but its cause is unknown. The disorder typically affects otherwise healthy adults age 40-60, progresses for a few months and then remains stable for decades. Muscles and nerves are normal, and most patients have periods of normal function – dark rooms, looking downward, even swimming under water are situations that patients report to be helpful.

Botulinum toxin injection can relieve the spasms, but eyelid apraxia often remains. Surgical lid elevation and botulinum toxin injection of the pretarsal orbicularis of the upper lid can be helpful, but static repositioning makes normal eye blinking and lid closure problematic. Functional electrical stimulation (FES) of the muscle that raises the eyelid (the levator palpebrae superioris or LPS), could provide these functionally blind patients with useful vision. Programmable, coordinated, binocular FES would be far superior to surgery, both functionally and cosmetically.
  • Scott AB, Miller JM, Namgalies TC (2018). Activating the levator to elevate the eyelid. In preparation (Authors' Cut PDFVideo).

Fellowships

In cooperation with the Strabismus Research Foundation, we are offering combined research-clinical fellowships to a few carefully-chosen candidates. Research would be conducted at Eidactics, and clinical experiences arranged with physicians at CPMC and UCSF. Funding is limited. Contact fellowships@eidactics.com.

Facilities

MAB

 
In Jan 2013 we relocated our offices and labs to San Francisco's landmark Medical Arts Building. Our new facilities are configured for micro-device development and fabrication, CAD and machining, immunohistochemistry, image analysis, and project management.

Our clinical studies are now conducted in collaboration with the Strabismus Research Foundation, at California Pacific Medical Center under supervision of their IRB, and our physiological studies are conducted with SRF at Bay Area CROs under supervision of their IACUCs.