Stargardt Disease Treatment with Topical Cholinergic Medication, Patient 247

Gerard M Nolan, MD September 2021



To demonstrate visual acuity and color vision improvement realized by a Stargardt disease patient resulting from topical cholinergic medication (TCM).


Early and sustained improvement in both visual acuity and color vision in a patient with Stargardt disease.   The improvement was a result of topical application of low dose echothiophate iodide (0.015%).   The gains in visual acuity and color vision have been maintained through a period of observation of one year.

Conclusions and Importance

TCM, low dose echothiophate iodide therapy produced significant and sustained gains in BCVA and color vision for this patient.   This compares favorably to the natural degradation to legal blindness in untreated Stargardt disease patients.   Low dose echothiophate iodide therapy potentially provides a treatment for Stargardt disease where none was previously available.


Today, Stargardt disease is the most common inherited single-gene retinal disease.  It usually has an autosomal recessive inheritance caused by mutations in the ABCA4 gene.1  Stargardt disease inevitably leads to significant and irreversible loss of vision.  Cholinergic stimulation (the parasympathetic nervous system) uses acetylcholine (ACh) at its receptors and synapses and is regulated by the enzyme acetyl cholinesterase.  Echothiophate iodide inhibits this enzyme acetyl cholinesterase and allows for the increase of endogenous acetylcholine.

This case history presents evidence of early and sustained improvement in visual acuity and color vision in a Stargardt Disease patient.  The improvement was a result of the application of TCM, low dose echothiophate iodide (0.015%).

Case Report / Findings

This case history presents evidence of improvement of visual acuity and color vision in a Stargardt Disease patient achieved by the application of low dose echothiophate iodide.

The present case involves a female patient diagnosed with Stargardt disease at age 19 in 1994.  This individual presented with no familial history of blindness or retinal disease.  The patient wore glasses since age 6 and contact lenses as a teenager.  She had a moderate myopia of -6.00 diopter.  The past medical history was significant for allergy to penicillin and seasonal allergies.  The patient’s identical twin (Patient 61) was diagnosed with Stargardt disease 6 months after her diagnosis.

Visual acuity declined at a steady progressive rate until age 23, at which point the patient experienced an abrupt drop in central and night vision and ceased driving.  In 1997, the patient presented at Baylor University Medical Center for genetic testing.  Test results revealed the presence of the ABCA4 gene consistent with Stargardt disease.

The patient initially presented for baseline testing at age 31 on March 7, 2006.  The patient is included in a 20 year, 309 Stargardt disease patient study.  The patient is also one of 22 patients in a one year, controlled proof-of-concept (POC) trial for Stargardt disease under the oversight of an Institutional Review Board (IRB).2  This ophthalmic clinical research was designed by PharmaLogic Development, Inc.3

Treatment Protocol

Prior diagnosis of Stargardt disease was verified via fluorescein angiography.  Best corrected visual acuity (BCVA) was established using the EDTRS system for distance and near vision and converted to logMAR for analysis.  Color vision was documented by the Ishihara 10 plate test.  The fluorescein angiogram revealed RPE dropout in both temporal and nasal retina.  The patient was classified as RPE Atrophy Stage IV.  The World Health Organization (WHO) visual impairment category was severe in the right eye and moderate in the left eye for both distance and near vision.

Following the initial consultation (visit 1), the patient returned the next day (visit 2.1) for retesting of baseline BCVA.  The patient was treated with a TCM, i.e., echothiophate iodide.  The patient received one drop of dilute (0.015%) echothiophate iodide in the lower cul-de-sac of both eyes and instructed to sit with eyes closed for one hour (visit 2.2).  The patient spontaneously reported an increase in overall vision brightness.  BCVA improved as follows,

Distance right eye improvement

6 letters (1.2 lines)

Distance left eye improvement

6 letters (1.2 lines)

Near right eye improvement

10 letters (2.0 lines)

Near left eye improvement

6 letters (1.2 lines)

Color vision remained at baseline, -1 plate (no control plate) for both eyes.  

The dosage used for treatment of this patient was one drop of 0.015% echothiophate iodide, administered to each eye every two days, immediately prior to sleep.   The patient returned every month for the first three months and every three months for the next nine months.

Case Report

The pre-treatment examination (visit 1) determined the patient's right eye distance BCVA to be 20/250-1 (1.12 logMAR) and left eye distance BCVA to be 20/125 (0.80 logMAR), eccentric fixation.  Right eye near BCVA was 20/320 (1.2 logMAR) and the left eye was 20/200+2 (0.96 logMAR).  The patient’s gaze was eccentric with particular difficulty in near vision focus.  Color vision was contrast-only, -1 plate (missed control plate) in both eyes.

Examination 24 hours after initial treatment (visit 3) revealed mild pupil narrowing of 1 mm (4 to 3 mm).  The patient's right eye distance BCVA had improved to 20/125-1 (0.82 logMAR).  Left eye distance BCVA improved to 20/80-1 (0.62 logMAR).  Near BCVA in the right eye improved to 20/160-1 (0.92 logMAR) and to 20/80+1(0.58 logMAR) in the left eye.  Color vision in both eyes improved to control.

The patient tolerated the medicine without any side effects.  None of the complaints of ocular burning, redness, irritation, dimming or blurring of vision, lacrimation or brow-ache associated with the traditional 0.25% and 0.125% concentrations of echothiophate iodide treatment of glaucoma have been reported by this patient.

Within the first month of therapy (visit 4), distance vision BCVA improved to 20/160-3 (0.96 logMAR) in the right eye and 20/80+1 (0.58 logMAR) in the left eye.  Near BCVA improved to 20/200 (1.00 logMAR) in the right eye and 20/125+1 (0.78 logMAR) in the left eye.  Color vision improved to 2 plates in the right eye and 3 plates in the left eye.

At one year (visit 9) distance BCVA was 20/125-1 (0.82 logMAR) in the right eye and 20/80-2 (0.64 logMAR) in the left eye.  Near BCVA improved to 20/160+1 (0.88 logMAR) in the right eye and 20/80-1 (0.62 logMAR) in the left eye.  Color vision was zero plates in the right eye and 5 plates in the left eye.

The patient exhibited significant BCVA and color vision improvement at one year:

Distance BCVA improvement

Right eye


lines (15 letters)

Left eye


lines (8 letters)

Near BCVA improvement

Right eye


lines (15 letters)

Left eye


lines (17 letters)

Color Vision Improvement

Right eye



Left eye



Table 1 summarizes the patient’s distance and near visual acuity and color vision for the duration of the study.

Stargardt Disease Patient 247 Vision Improvements


Dilute echothiophate iodide provided an effective, non-surgical therapy for this Stargardt disease patient.  After visit 3, the patient left the office and could identify a green, John Deere tractor parked across the street.  While shopping at a local mall, she remarked to her family that the colors of clothes were much brighter here than at home.  Her mother replied that the colors were the same as at home.  At the hotel, while eating breakfast, she could see through the windows and recognize automobiles passing by.  Being able to look through an automobile window and see street signs, traffic lights and pedestrians walking on the sidewalk was new to her.

Returning home, she noticed her father had facial wrinkles.  She could the see the ears and noses of her children.  She could also see their dirty faces and recognize soiled diapers of her youngest child.  She took up gardening and shopping.  Cooking became easier.  Watching television was possible and she was now able to qualify for a restricted driver’s license.

The patient’s vision gains have restored her independence and allowed her to be more active in the community.  She has become an advocate for individuals suffering from blindness due to macular degeneration and Stargardt disease.  She summarized her treatment success by stating: “It was like being normal, like everyone else!”

For the last 15 years, the patient has been followed by her local vitreal retinal specialist.  The patient has maintained the vision improvement observed during the treatment period.  The patient continues to be independent, active in the community and maintains a current driver’s license.

In summary, this case study presents evidence of BCVA and color vision improvement for this Stargardt disease patient resulting from the application of low dose echothiophate.  The treatment resulted in a marked improvement of quality-of-life.


Stargardt disease is one of a number of degenerative retinal diseases, including dry age-related macular degeneration and retinitis  pigmentosa, which may respond to TCM therapy.  If this turns out to be the case, this therapy may hold the potential to lessen the disability from a number of blinding retinal diseases.

The exact mechanism of action of echothiophate iodide in Stargardt disease patients is not yet known.  Perhaps, dilute echothiophate iodide makes endogenous ACh more available to diseased neuroreceptor populations across the retina.  Increased ACh levels may amplify the synaptic potential of the surviving photoreceptors and ganglion cells, making it possible for these reduced populations to achieve threshold and resume the propagation of visual information to the brain.  This effect would parallel previously described mechanisms of drug action in other neurological diseases, such as Parkinsonism, Alzheimer’s Disease and Clinical Depression.

Topical cholinergic medications, echothiophate iodide, pilocarpine, etc., have been a staple to treat glaucoma and strabismus.  Recently, the use of several different cholinergic therapeutics has been expanded to include treatment of presbyopia.  This case study illustrates a single Stargardt disease patient treated with a cholinergic medication, i.e., low dose (0.015%) echothiophate iodide.  The patient showed initial and long term improvement which has been maintained through a period of observation of more than 15 years.  The treatment resulted in a marked improvement of the patient’s quality-of-life.

This compares favorably to the natural degradation of visual acuity often leading to legal blindness caused by this untreatable disease.  Hopefully, the ophthalmology community will become aware of this Stargardt disease treatment regimen and add it to their tools for the treatment of this disease.

Patient consent

Written informed consent was obtained from the patient for publication of this case report.  This report does not contain any personal identifying information.


  1. Michaelids M, Hunt DM, Moore AT.  The genetics of inherited macular dystrophies.  J Med Genet.  2003;40(9):641-650.
  2. IRB file number - 05175-01 (November 23, 2005) A Pilot, open-label study of low dose ocular echothiophate iodide for the treatment of Stargardt’s [sic] Disease.  Principal Investigator Number - 5575-001.  Sponsor - Independent Review Consulting, Inc.  (IRC), Corte Medera, California
  3. PharmaLogic Development, Inc, San Rafael, California Ophthalmic Research and Development

Abbreviations and Acronyms:

ETDRS  =  Early Treatment Diabetic Retinopathy Study;   IRB  =  International Review Board;   RPE  =  retinal pigment epithelium;  TCM = topical cholinergic medication; WHO  =  World Health Organization