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Kimberly Nolan, O.D. Dorchester House Multi-Service Center Dorchester, MA Resident’s Day Submission: Academy 2008 Splenda Retinopathy: A case report Abstract A potential connection between excessive sucralose (Splenda) consumption and retinopathy is witnessed in a healthy twenty-four year-old female who presents with a “decreased sharpness” to her distance vision. Case Report Outline I. Case History a. Patient Demographics: Twenty-four year old white female b. Chief complaint: Constant “decreased sharpness” (OD=OS) in her distance vision x 2 yrs. i. She first noticed the change one-year prior (August 2007) for which she visited an optometrist who told her that her vision changes were likely a temporary problem. She was prescribed reading glasses at that visit. The reading glasses did not help with the change in distance vision either immediately or over time; therefore, the patient sought a second opinion. c. i. Ocular history: Migraine with aura causing a bilateral central vision loss lasting 20 minutes. 1. Noted on two separate occasions after ingesting an excessive amount of sucralose at one time. 2. Both instances occurred after her aforementioned optometry appointment in August 2007 and when she presented to our clinic in August 2008. ii. Medical history: Migraine headaches iii. Allergies: cats iv. Family ocular history: cataracts. 1. No family history of glaucoma, maculopathy or blindness. d. Medications: Ortho-Tri cyclin lo e. Social history: 2.5 years of daily excessive Splenda consumption i. She admitted to ingesting 50-80+ grams of Splenda / day ii. (1 packet= 1 gram). II. Pertinent findings a. Clinical i. VA 20/20- OD and OS. ii. Entrance testing within normal limits iii. Slit lamp exam unremarkable OU iv. Dilated fundus exam revealed diffuse pigment changes and the appearance of thin, irregular pigment granules in her maculae. v. OCT revealed thinner than average foveal and central foveal thickness OU1 b. Physical i. Weight: 133.2 lbs = 60.4 Kg ii. Height: 62.5” iii. Blood Pressure: 106/60 c. Laboratory Studies: i. Blood work revealed a slightly fatty liver on (ALT=54 IU/L), slightly elevated C Reactive Protein (11 Mg/L), and slightly reduced iron saturation of 13 (Normal range= 15-55). ii. All other blood work unremarkable including: triglycerides; serum cholesterol, serum sodium, serum potassium, serum chloride, serum phosphorus, BUN, serum creatinine, BUN/Creatinine ratio; serum uric acid, bilirubin, AST, GGT, alkaline phosphate, serum iron, iron binding capacity, serum total protein, serum albumin, globulin, A/G ratio, Carbon dioxide total, UIBC, glomerulus filtration rate, TSH, hemoglobin, hematocrit, RBC, MCV, MCH, MCHC, RDW, WBC, urinalysis, vitamin D. iii. Blood work also negative for: Lyme disease, Toxoplasmosis, Rickettsia IgG, Rickettsia IgM, Rickettsia Typhi IgM, Rickettsia Typhi IgM, Rickettsia Typhi IgG III. Differential Diagnosis a. Inherited macular disease i. Stargardt disease ii. Cone dystrophy iii. Pattern dystrophy iv. North Carolina macular dystrophy v. Butterfly-Shaped macular dystrophy 1. Presents in second to third decade typically by chance but may have accompanying complaints of decreased central vision. b. Ocular side effects from oral contraceptive c. Acute macular neuroretinopathy d. Batten disease e. Toxoplasmosis – a differential for the chorioretinal scar OD i. Proven negative by blood work IV. Diagnosis and discussion a. E.D. is a healthy 24-year-old white female with a history of migraine headache with aura. She has no further history of ocular disease or systemic disease (confirmed by blood work). Her family ocular history is b. c. d. e. significant for cataracts. Her social history includes ingesting excessive amounts of sucralose (Splenda) on a daily basis for two and a half years. Average daily consumption was estimated to be 50-80 grams of Splenda / day (1 packet= 1 gram). She presented to an optometrist one year ago with complaints of a “decrease in sharpness” to her central distance vision. She was subsequently given reading glasses. The vision changes persisted and only after re-evaluating her dietary habits did she begin to question her excessive Splenda consumption as being related not only to the dimming of her vision but also as a trigger to her migraine headaches. Our patient began excessive sucralose consumption when she started the South Beach diet. She reports enjoying her beverages “extremely sweet” and was also using sucralose in place of sugar for any cooking or baking she did. There have been no published articles that suggest a connection between excessive sucralose consumption and retinopathy; however, countless personal accounts of blurred vision have been reported with high daily intake of sucralose. An article has been published in Headache that discusses a case report of a patient whose migraines were attributed to sucralose consumption.2 Sucralose (Splenda) toxicity i. Sucralose (trichlorogalactosucrose or Splenda) is an artificial sweetener that has been used for the past ten years, after FDA approval was granted in April 1998. FDA and manufacturer studies indicate that sucralose is a safe alternative to sugar; 3 however, not all consumers agree. ii. It is made from sucrose in a five-step process that includes replacing hydroxyl groups with three chlorine molecules. iii. Estimated daily intake (EDI) in humans is 1.1 mg/kg/day. Acceptable daily intake is 16 mg/kg/day. Highest no adverse effects limit in is 1500 mg/kg/day 4. The latter two quoted daily intakes were determined with animal (rat) studies and have not been duplicated in humans. 1. Our patient was consuming approximately 827- 1324.50 mg/kg/day iv. While studies have proven that sucralose is safe in animals, there have been no long-term studies with high daily intake of the chemical in either animals or humans. Chloroquine retinopathy i. Well-known and clinically proven Chloroquine retinopathy is related to the dose a patient is taking. Symptoms and retinal changes include: altered color vision, Scotoma: central, paracentral, or peripheral, bulls-eye macular lesion, arteriolar narrowing, vascular sheathing. ii. Other known drug-induced maculopathies: 1. Chlorpromazine, thioridazine (anti-psychotic), tamoxifen (breast cancer treatment), canthaxanthin (carotenoid used to enhance sun tanning), methoxyflurane (inhalant anesthetic), nitrofurantoin (antibiotic), nicotinic acid (cholesterollowering medication), desferrioxamine mesylate (iron overload treatment). V. Treatment, management a. Discontinue Splenda b. Further blood-work to rule out other causes c. Monitor and patient education to report changes in vision and/or color vision after Splenda is discontinued. d. Monitor retinal changes with fundus photos and OCT VI. Conclusion a. There have been no long-term studies performed on the safety profile of sucralose when consumed in excess as occurred in our patient. This case proves a potential link between long-term, high-dose daily intake of sucralose and retinopathy. Further investigation and research should be performed to determine potential side effects of excessive sucralose consumption. VII. References 1. Chan, Annie, MD; Ducker, Jay S.; Ko, Tony H.; Fujimoto, PhD; Schuman, Joel S., MD. Normal Macular Thickness Measurements in Healthy Eyes Using Stratus Optical Coherence Tomography. Archives of Ophthalmology. 2006; 124: 193-198. 2. Patel, Rajendrakumar et al. Popular Sweetener Sucralose as a Migraine Trigger. Headache. 2006. Pg. 1303,1304. 3. Department of Health and Human Services. Food and Drug Administration. Food Additives Permitted for Direct Addition to Food for Human Consumption; Sucralose. Docket number 87F-0086. April 3, 1998. 4. Frank, Genevieve. Sucralose: An Overview. Undergraduate Research Journal for the Human Sciences. 2001. 5. Kanski, Jack J. Clinical Ophthalmology. 6th edition. 2007. Pg.505, 844, 672 6. Kaiser, Peter K; Friedman, Neil et. al. The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. “ 2nd Edition. 2004 . Pg. 344-347. 7. Kunimoto, Derek M.D.; Kanitkar, Kunal M.D. Makar, Mary M.D. (ed.). The Wills Eye Manual. 4th edition. 2004. Pg. 283-287.