Amblyopia is the leading cause of visual loss in children, affecting 2% to 3% of the population.1 The primary and best treatment has been occlusion of the dominant eye,2 but the speed and stability of improvement depends on the age when treatment starts because efficacy decreases after 6 years of age.3 In addition, many older children and teenagers fail to achieve near normal visual acuity. Only 23% of children with severe amblyopia and 36% of children with moderate amblyopia between 7 and 13 years of age achieve a visual acuity of 20/40 or better.4
As a result, levodopa/carbidopa has been explored as an adjunct to conventional therapy. Dopamine, a metabolite of levodopa, is a neurotransmitter known to influence the visual system at both the retinal and cortical level,5 whereas the addition of carbidopa prevents the breakdown of levodopa peripherally, allowing more to cross the blood–brain barrier. Leguire et al. initially found administering levodopa had an immediate impact on visual acuity in amblyopic children several hours after ingestion using a large single dose,6 although in a later study they found a smaller dose of levodopa/carbidopa had an approximately one-line improvement with fewer side effects.7 In a subsequent 3-week double-blinded, placebo-controlled, single dose study and a 7-week open clinical trial, they found combining a small dose of levodopa/carbidopa with part-time occlusion resulted in a sustained 1.2 line and 37% improvement in visual acuity, respectively.8,9 Adults with amblyopia have also shown improvement in visual acuity after levodopa administration without occlusion.10–12
Given these promising initial results, several studies to date have explored the benefit of supplementing conventional occlusion therapy with levodopa/carbidopa.5,8,13–15 However, they have primarily studied children younger than 17 years. The oldest reported individual receiving combination therapy was 24 years of age, and the study found no improvement with levodopa/carbidopa. To our knowledge, we describe the oldest patient documented in the literature to have shown improvement in visual acuity using levodopa/carbidopa while effectively undergoing full-time occlusion due to a glaucomatous right eye with no light perception. Informed consent was obtained from the patient for this case to be published.
The ophthalmic records were reviewed for a 46-year-old man who presented for drug therapy for refractory amblyopia of the left eye. A complete ocular history and examination were performed and an assessment of his vision was done on follow-up after being prescribed levodopa/carbidopa.
The patient was referred from his current ophthalmologist because he was interested in potential drug therapy for amblyopia in his left eye. He had bilateral congenital cataracts, undergoing cataract extraction of the right eye at age 1 year and the left eye at age 3 years. He was diagnosed as having glaucoma in his right eye at age 12 years, undergoing trabeculectomies in 1980 and in 2010. The latter was notable for a complication of choroidal hemorrhage. Medication included latanoprost 0.005% solution (Xalatan; Pfizer, New York, NY) every night and prednisolone acetate 1% ophth suspension (Pred Forte; Allergan, Irvine, CA) two to three times a day in his right eye for comfort purposes instead of his glaucoma. Visual acuity in his right eye progressed from light perception to no light perception 5 years ago.
On examination, he had no light perception in his right eye and a best-corrected visual acuity of 20/50−2 in his left eye with no pinhole improvement. He was wearing a +13.00 rigid, gas permeable contact lens in his left eye. The remainder of his left eye examination was notable for a clear cornea with few endothelial changes, a deep and quiet anterior chamber, an iris with a surgical pupil, aphakia, and an unremarkable fundus examination with a full but healthy nerve. He was given levodopa/carbidopa 100/25 mg at a dose of half tablet three times a day (2.28/0.51 mg/kg/d) for 16 weeks.
On the 3-month follow-up visit, the patient noted a slight improvement in his vision, found colors brighter and more recognizable, and was able to process visual information faster. Best-corrected visual acuity in his left eye was 20/40−2 and improved to 20/30−2 with pinhole. This was a full two-line improvement in 3 months. Per the patient’s request, his levodopa/carbidopa dose was increased to one tablet three times a day. On the 6-month follow-up visit, his visual acuity was 20/30−1 in his left eye, a one-letter improvement over his prior visit. The levodopa/carbidopa was tapered off after this visit and visual acuity in his left eye stabilized at 20/30−1 with no medication at the 9-month and 1-year follow-up visits.
Several studies to date have shown improvement in visual acuity using levodopa/carbidopa alone in children6,7 and levodopa/benzerazide,10 levodopa,11 and levodopa/carbidopa12 in adults. However, subsequent clinical trials assessing the effect of supplementing conventional occlusion therapy with levodopa/carbidopa or placebo have shown mixed results, either finding significantly more improvement when levodopa/carbidopa is added5,8,13 or detecting no appreciable benefit.14,15 The uncertainty remains in trials that have analyzed the effect of occlusion therapy in conjunction with levodopa/carbidopa with one finding significantly better results when patching is added to levodopa/carbidopa,16 whereas another found no added benefit of occlusion therapy.17 A 7-week open clinical trial of administering levodopa/carbidopa with part-time occlusion in older children with amblyopia also found a significant improvement in visual acuity, although it lacked a control group.9
However, there is a drawback in comparing these studies because each analyzes a distinct patient population, employs different methods, and performs varied statistical analyses. In the three double-blinded, randomized controlled trials that found more improvement of levodopa/carbidopa with occlusion over occlusion alone, they differed in amblyopia types (mixed8 vs strabismic5,13), whether they had received prior treatment13 or not,5 levodopa/carbidopa dosing (1.44/0.36,8 1.50/3.75,5 and 0.5113 mg/kg/d), part-time8,13 versus full-time5 patching, length of treatment (3 weeks,8 3 months,5 and 1 week13), and statistical analysis performed,5 although they studied similar age groups (6 to 14,8 3 to 12,5 and 7 to 1713 years) and none of them accounted for differences in baseline visual acuity. In the two studies that found no appreciable benefit of adding levodopa/carbidopa to occlusion therapy, they differed in study type (double-blinded, randomized controlled14 vs prospective interventional15), age groups (6 to 1814 vs 3 to 2415 years), amblyopia types (strabismic and anisometropic14 vs mixed15), dosing (1.86/0.46514 vs 6.25 to 8.3/10:115 mg/kg/day), part-time15 versus full-time14 patching, and length of treatment (4 weeks levodopa/carbidopa with 3 months patching14 vs 6 weeks15), although both studies included patients who received no prior treatment and accounted for differences in baseline visual acuity. In the two double-blinded, randomized controlled studies that analyzed the effect of occlusion therapy on levodopa/carbidopa administration, they differed in age groups (7 to 1216 vs 4 to 2217 years), dosing (3.06/0.7516 vs 1.50/0.37517 mg/kg/d), and part-time16 vs full-time17 patching, although they both were 7 weeks in duration and accounted for differences in baseline visual acuity.
Nevertheless, these studies do share some similar findings in addition to other unique conclusions. These include maintained visual acuity on follow-up5,8,16,18 and significant improvement in contrast sensitivity of the amblyopic eye8,16 for those treated with both levodopa/carbidopa and occlusion therapy. No difference was found between strabismic and anisometropic amblyopes in response to treatment regardless of regimen.7,9,14 Dadeya et al.5 found that significantly more children younger than 8 years improved more than two lines in visual acuity compared to those older than 8 years, although Leguire et al.7 and Mohan et al.17 found no significant relationship between age and mean improvement in visual acuity. However, this discrepancy may be attributed to the difference in their statistical methods, sample size, and the latter two studies’ inclusion of treatment failures. Nevertheless, levodopa’s immediate and substantive effect on neuronal plasticity5–17 translates into shorter latency in response to occlusion,5 making for better compliance with a combined regimen.14
Although levodopa alone has already shown promising short-term improvement in middle-aged adults,10–12 the above clinical trials fail to assess the impact of levodopa/carbidopa in combination with occlusion therapy on sustained visual improvement in this population. Our case is anecdotal, but it is noteworthy for a sustained two-line improvement in a 46 year old who had continuously been full-time patched via a glaucomatous right eye. By controlling for pharmacologic intervention, it suggests a dose of levodopa/carbidopa in line with prior studies with a fully compliant patient may result in a significant clinical improvement in adults.
A future clinical trial that examines this patient population while systematically accounting for longer patching length, levodopa/carbidopa dosing, treatment duration, prior treatment, amblyopia type, visual acuity, contrast sensitivity, compliance, and latency to response may widen the age group that may benefit from pharmacologic intervention and better understand its effect.
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- von Noorden GK. Binocular Vision and Ocular Motility: Theory and Practice of Management of Strabismus, 5th ed. St. Louis, MO: Mosby-Year Book; 1996:216–54, 512–20.
- Fulton AB, Mayer DL. Esotropic children with amblyopia: effects of patching on acuity. Graefes Arch Clin Exp Ophthalmol. 1988;226:309–312. doi:10.1007/BF02172956 [CrossRef]
- Scheiman MM, Hertle RW, Beck RW, et al. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol. 2005;123:437–447. doi:10.1001/archopht.123.4.437 [CrossRef]
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- Leguire LE, Walson PD, Rogers GL, Bremer DL, McGregor ML. Longitudinal study of levodopa/carbidopa for childhood amblyopia. J Pediatr Ophthalmol Strabismus. 1993;30:354–360.
- Leguire LE, Walson PD, Rogers GL, Bremer DL, McGregor ML. Levodopa/carbidopa treatment for amblyopia in older children. J Pediatr Ophthalmol Strabismus. 1995;32:143–151.
- Gottlob I, Stangler-Zuschrott E. Effect of levodopa on contrast sensitivity and scotomas in human amblyopia. Invest Ophthalmol Vis Sci. 1990;31:776–780.
- Gottlob I, Charlier J, Reinecke RD. Visual acuities and scotomas after one week levodopa administration in human amblyopia. Invest Ophthalmol Vis Sci. 1992;33:2722–2728.
- Gottlob I, Wizov SS, Reinecke RD. Visual acuities and scotomas after 3 weeks’ levodopa administration in adult amblyopia. Graefes Arch Clin Ophthalmol. 1995;233:407–413. doi:10.1007/BF00180943 [CrossRef]
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- Leguire LE, Komaromy KL, Nairus TM, Rogers GL. Long-term follow-up of L-dopa treatment in children with amblyopia. J Pediatr Ophthalmol Strabismus. 2002;39:326–330.