Low-Level Laser Therapy Improves Visual Acuity in Adolescent and Adult Patients with Amblyopia

Abstract

Objective: The purpose of this study was to examine the effects of low-level laser therapy (LLLT) on visual acuity in adolescent and adult patients with amblyopia. Background data: Currently, amblyopia can be treated successfully only in children. Methods: In this single-blinded, placebo-controlled study, 178 patients (mean age 46.8 years) with amblyopia caused by ametropia (110 eyes) or strabismus (121 eyes) were included. For LLLT, the area of the macula was irradiated through the conjunctiva from 1 cm distance for 30 sec with laser light (780 nm, 292 Hz, 1:1 duty cycle; average power 7.5 mW; spot area 3 mm²). The treatment was repeated on average 3.5 times, resulting in a mean total dose of 0.77 J/cm². No occlusion was applied, and no additional medication was administered. Best corrected distant visual acuity was determined using Snellen projection optotypes. In 12 patients (12 eyes), the multifocal visual evoked potential (M-VEP) was recorded. A control group of 20 patients (20 eyes) received mock treatment. Results: Visual acuity improved in ∼90% of the eyes treated with LLLT (p<0.001), increasing by three or more lines in 56.2% and 53.6% of the eyes with amblyopia caused by ametropia and strabismus, respectively. The treatment effect was maintained for at least 6 months. The mean M-VEP amplitude increased by 1207 nV (p<0.001) and mean latency was reduced by 7 msec (p=0.14). No changes were noted in the control group. Conclusions: LLLT led to a significant improvement in visual acuity in adolescent and adult patients with amblyopia caused by ametropia or strabismus.

Introduction

A m blyopia (also known as “lazy eye”) is the most common form of impaired vision in children affecting nearly 2–4 % of the population.^1,2 There are two major causes of amblyopia: (1) strabismus, a misalignment of the eyes, and (2) ametropia, a severe difference of the refractive status between the two eyes. Both conditions may cause substantially different images, which cannot be fused by the brain. Therefore, the blurrier image is suppressed leading to poor visual development, also known as amblyopia in the “blurrier” eye.

Current treatment of amblyopia involves optimal correction of refractory anomalies followed by occlusion of the leading eye or penalization.^3
-5 Generally, vision can be improved in children only up to the age of 9 years. If therapy starts later, full visual acuity and binocularity can be achieved only in rare cases. In adult patients, treatment of amblyopia can only aim at improving the quality of life, for example, by eliminating any work-related disadvantages. Various therapeutic approaches have been tested in adult patients but without long-term success.

Here, we present first evidence that low-level laser therapy (LLLT) may improve visual acuity in adolescent and adult patients with ametropic or strabismic amblyopia.

Materials and Methods

Study design and patients

This single-blinded, placebo-controlled, interventional, noninvasive study was conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from all patients before enrollment. Data were collected during a 7-year period (maximal follow-up of 13 years) and retrospectively evaluated.

Patients ≥12 years of age with ametropic or strabismic amblyopia were included if they presented with a distant visual acuity of ≤20/30 Snellen after optimal correction. Patients were excluded if they had other concomitant eye or other systemic diseases that could impair vision.

Laser treatment

A continuous wave (cw)-type semi-conductor laser diode (780 nm) mounted with collimating optics (round laser spot area at 1 cm distance: 3 mm²) in a handheld casing, was used for LLLT. The laser was driven by an apparatus that provided low-frequency switching of the laser beam (292 Hz, 1:1 duty cycle) and automatic control of 7.5 mW average output power (Bimed, Munich, Germany). The average laser output was measured before each treatment using an external laser power output meter (Laser components GmbH, Groebenzell, Germany). The effective minimal laser power of 7.5 mW had been determined previously.⁶

Laser irradiation was applied to the macula by guiding the beam of the laser diode at 1 cm distance above the eyeball while the eye was maintained in adduction. If necessary, eyelids were manually fixed. Each treatment took 30 sec with a dose of 0.22 J/cm². Three to four (mean 3.5) treatments were performed during 2 weeks (mean total dose of 0.77 J/cm²).

Twenty patients (20 eyes) were randomly selected to receive mock treatment (control group); the laser beam was directed above the nose without contacting the eye. An acoustical signal after every 10 sec was perceived as treatment by the patients.

Ophthalmological examinations

A biomicroscopical and ophthalmoscopical examination was conducted at study inclusion (baseline), before each treatment, and at the end of the study. These examinations were performed under comparable conditions with respect to time of examination and examiner. Best corrected distant visual acuity was assessed by projection of Snellen optotypes (American Optical, U.S.A.) at a 20-foot distance after optimal correction of refraction. Only unknown optotypes were presented to prevent patients from learning them. In a subgroup of 12 patients (12 eyes) we recorded an M-VEP (according to methodological guidelines available at www.iscev.org) using a Retiport system (Roland Consult, Germany).

To assess treatment safety and tolerability, we examined patients' eyes before and after each treatment session, and asked patients about their general well-being by non-leading questions.

Data analysis

Data on visual acuity were transformed into logarithmic minimal angle resolution (log MAR). Data were analyzed retrospectively categorizing the results as no change, improvement, or worsening. A t test for paired samples was used to examine the statistical significance of changes after completion of LLLT compared to baseline.

Results

Demographic and baseline characteristics

We included 178 patients (75 women, 103 men) with a mean age of 46.8 years (range: 13–72 years) in the study. Thirteen out of these 178 patients were adolescents, that is, 13–18 years old (6 women, 8 men). Two-hundred thirty-one eyes with amblyopia (118 right and 113 left eyes) were treated and evaluated. Amblyopia was caused by ametropia in 110/231 eyes and by strabismus in 121/231 eyes. In 53 patients amblyopia affected both eyes. The control group included 20 patients (14 women, 6 men) with a mean age of 38.6 years (range: 18–64 years) and 20 eyes with amblyopia caused by ametropia (n=10) and strabismus (n=10).

Visual acuity

LLLT improved best corrected distant visual acuity in 100/110 eyes with ametropic amblyopia (91%; p<0.001). Visual acuity increased by 1, 2, 3, 4, 5, 6, and 7 rows in 6%, 28%, 23%, 14%, 13%, 4%, and 3% of the eyes, respectively. In 10 eyes (9%) visual acuity remained unchanged (Table 1).

Table 1.

Visual Acuity Before and After Low-Level Laser Therapy (LLLT) in 110 Eyes with Amblyopia Caused by Ametropia

	Before LLLT
Visual acuity	20/400	20/200	20/100	20/80	20/70	20/60	20/50	20/40	20/30	log MAR	Sum
After LLLT
20/400	3										3
20/200	1	3								+1.0	4
20/100		2								+0.7	2
20/80	1	6	1	1						+0.5	9
20/70		2	4	1	3					+0.4	10
20/60				3						+0.3	3
20/50		1	1	14	10					+0.2	26
20/40			1	4		1	2			+0.15	8
20/30		3			4	1	3			+0.1	11
20/25					3	1	1	2		+0.05	7
20/20					3	2	4	2	2	0	13
20/16						1	7	2	4	−0.1	14
Sum	5	17	7	23	23	6	17	6	6		110

Best corrected distant visual acuity was measured at a distance of 20 feet using American Optical Snellen optotypes. The change in visual acuity is presented in terms of logarithmic minimal angle resolution (log MAR).

In patients with strabismic amblyopia, visual acuity improved in 107/121 eyes by one or more rows (89%; p<0.001). Visual acuity increased by 1, 2, 3, 4, 5, 6, and 7 rows in 20%, 15%, 19%, 16%, 14%, 3%, and 2% of eyes, respectively. In 14 eyes (11%) visual acuity remained stable (Table 2). No changes in the visual acuity were observed in the control group.

Table 2.

Visual Acuity Before and After Low-Level Laser Therapy (LLLT) in 121 Eyes with Strabismic Amblyopia

	Before LLLT
Visual acuity	20/400	20/200	20/100	20/80	20/70	20/60	20/50	20/40	20/30	log MAR	Sum
After LLLT
20/400	7										7
20/200	11	3								+1.0	14
20/100	2	8	1							+0.7	11
20/80	3	4								+0.5	7
20/70	5	5	5		1					+0.4	16
20/60	2		2	3	1	1				+0.3	9
20/50	2	3	3	8	2	4	1			+0.2	23
20/40					1					+0.15	1
20/30				1	6	2				+0.1	9
20/25				1		1	1			+0.05	3
20/20				2		3	3		2	0	10
20/16							8	2	1	−0.1	11
Sum	32	23	11	15	11	11	13	2	3		121

Best corrected distant visual acuity was measured at a distance of 20 feet using American Optical optotypes (Snellen). The change in visual acuity is presented in terms of logarithmic minimal angle resolution (log MAR).

Generally, the increase in visual acuity after LLLT tended to be faster and more pronounced in adolescent patients (aged ≤18 years) in comparison to adult patients (aged >18 years) with ametropic or strabismic amblyopia (data not shown).

One patient with ametropic and esotropic amblyopia was followed for 13 years. The visual acuity of the better eye was maintained at the level obtained after the initial LLLT (from 20/30 to 20/20), over a period of 10 years. The visual acuity of the strabismic (esotropic) eye had returned to the initial visual acuity of 20/100 but reached again a maximum of 20/25 after repeated treatments (Fig. 1).

FIG. 1.

Long-term effects of low-level laser therapy in a patient with amblyopia. Measurements of best corrected distant visual acuity in a patient (aged 13 years at the beginning of therapy) with ametropic amblyopia (left eye, upper curve) and esotropic amblyopia (right eye, lower curve). (A) Baseline and after treatment session 1 to 5; (B) 10 months post-baseline, before and after repeated treatments (1 treatment); (C) 39 months post-baseline, before and after repeated treatments (3 treatments); (D) 13 years post-baseline, before and after repeated treatment (4 treatments).

M-VEP

The amplitudes of the M-VEP recorded in 12 patients (12 eyes), ranged from 558 to 6543 nV and from 1471 to 6794 nV before and after LLLT, respectively. The mean amplitude increased by 1207 nV from 2412 nV at baseline to 3619 nV after LLLT (+50%; p<0.001). M-VEP latencies ranged from 116 to 195 msec (Table 3). A representative example of the change in M-VEP is shown in Fig. 2.

FIG. 2.

Multifocal visual evoked potential (M-VEP) before and after low-level laser therapy (LLLT) in a patient with strabismic amblyopia. LLLT (6 treatments) of the left eye (lower curve) in a 65-year old patient with strabismic amblyopia increased best corrected distant visual acuity from 20/70 to 20/30 and M-VEP amplitude by 1094 nV. No changes were noted for the untreated right eye (upper curve).

Table 3.

Multifocal Visual Evoked Potential and Visual Acuity Before and After Low-Level Laser Therapy (LLLT) in 12 Eyes with Amblyopia

Eye	Amplitude [nV]			Latency [msec]			Visual acuity
ID no.	Before LLLT	After LLLT	Change [%]	Before LLLT	After LLLT	Change [%]	Before LLLT	After LLLT
1	2438	3532	44.9	128	128	0.0	20/63	20/32
2	1280	1903	48.7	121	116	−4.1	20/80	20/25
3	1267	1471	16.1	120	120	0.0	20/40	20/20
4	2173	3091	42.2	120	120	0.0	20/200	20/25
5	1803	2248	24.7	125	125	0.0	20/40	20/16
6	1445	2019	39.7	125	125	0.0	20/40	20/32
7	2295	4469	94.7	125	125	0.0	20/32	20/25
8	4296	6794	58.1	195	153	−21.5	20/63	20/32
9	6543	7530	15.1	195	195	0.0	20/80	20/16
10	558	1847	231.0	120	120	0.0	20/100	20/32
11	2248	3916	74.2	160	125	−21.9	20/40	20/16
12	2592	4603	77.6	125	125	0.0	20/25	20/16
Mean	2412	3619	+50.0	138	131	−5.1	20/67	20/23

Safety and tolerability

Overall, LLLT was safe and well tolerated. There were neither local nor systemic adverse effects. No case of diplopia occurred. Ophthalmoscopic examinations revealed no visible morphological changes of the macula after LLLT.

Discussion

Amblyopia is a frequent cause of impaired vision, which can be successfully treated only in children. So far, there is no therapeutic option for adolescents or adults who have missed this critical time interval. We present here first evidence that LLLT may improve visual acuity even in these patients.

A statistically significant improvement in best corrected distant visual acuity was observed after LLLT in 90% of the eyes with amblyopia in adults. In some eyes, visual acuity even reached 20/20. The magnitude of the improvement appeared to correlate with baseline visual acuity. Patients with strabismic amblyopia who did not respond to LLLT (11%) had severe amblyopia with poor visual acuity (≤20/200) and eccentric fixation.

Additional treatments helped to regain the once initially achieved improvement in visual acuity in patients who experienced a recurrent loss of vision. We therefore suggest regular controls and, if necessary, repeated LLLT (at first every 3 months, then every year) to stabilize the initial improvement of visual acuity.

M-VEP revealed a statistically significant increase of the amplitude. This increase did not correlate with the functional improvements. This may be explained by the fact that the amplitude is subject to various influences, and is therefore less reliable than the latency. The shortening of the latency was slight and not statistically significant.

The exact mechanisms of the effects of LLLT are not elucidated.⁷ Experimental studies found that laser light stimulated metabolic activities and cellular protein synthesis by increasing the synthesis of adenosine-3-phosphate.⁸ Eyes with amblyopia may also benefit, similarly to eyes with age-related macular degeneration (AMD),⁶ from the direct stimulation by laser light causing a hyperpolarisation. Such stimuli were shown to promote interneuronal communication and function, probably by synaptogenesis and formation of “spins”.⁹

Conclusions

LLLT may improve best corrected distant visual acuity and amplitude of the M-VEP in adolescent and adult patients with ametropic and/or strabismic amblyopia. The rapid improvement of visual acuity is associated with fewer treatments and control examinations and is therefore very economic. LLLT is not destructive or painful, and can easily be applied in combination with other therapies, or even as prophylaxis to avoid the development of amblyopia. The short duration of LLLT and lack of occlusion or additional drug treatments is expected to positively affect patient compliance.

This explorative study was undertaken to gain first experiences in this new field. Future trials are required to compare and establish the optimal treatment modalities using randomized, controlled, and double-blinded study designs and an appropriate number of study subjects.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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