Effectiveness of Laser Refractive Surgery to Address Anisometropic Amblyogenic Refractive Error in Children

Abstract

Purpose:

To review the published literature assessing the safety and effectiveness of laser refractive surgery to treat anisometropic amblyogenic refractive error in children aged ≤ 18 years.

Methods:

A literature search of the PubMed database was conducted in October 2021 with no date limitations and restricted to publications in English. The search yielded 137 articles, 69 of which were reviewed in full text. Eleven articles met the criteria for inclusion and were assigned a level of evidence rating.

Results:

The 11 included articles were all level III evidence and consisted of 1 case-control study and 10 case series. Six studies used laser-assisted in situ keratomileusis (LASIK), 1 used photorefractive keratectomy (PRK), 1 used refractive lenticule extraction/small incision lenticule extraction, and the rest used a combination of LASIK, PRK, laser epithelial keratomileusis (LASEK), or refractive lenticule extraction/small incision lenticule extraction. Five studies enrolled patients with anisometropic myopia, 2 studies enrolled patients with anisometropic hyperopia, and the remainder were mixed. Although all studies demonstrated an improvement in best-corrected visual acuity (BCVA), the magnitude of improvement varied widely. As study parameters varied, a successful outcome was defined as residual refractive error of 1 diopter (D) or less of the target refraction because this was the most commonly used metric. Successful outcomes ranged between 38% and 87%, with a mean follow-up ranging from 4 months to 7 years. Despite this wide range, all studies demonstrated an improvement in the magnitude of anisometropia. Regression in refractive error occurred more frequently and to a greater degree in myopic eyes and eyes with longer follow-up, and in younger patients. Although one study reported 2 free flaps, most studies reported no serious adverse events. The most common complications were corneal haze and striae.

Conclusions:

Findings from included studies suggest that laser refractive surgery may address amblyogenic refractive error in children and that it appears to decrease anisometropia. However, the evidence for improvement in amblyopia is unclear and long-term safety data are lacking. Long-term data and well-designed clinical studies that use newer refractive technologies in standardized patient populations would help address the role of refractive surgery in children and its potential impact on amblyopia.

The American Academy of Ophthalmology prepares Ophthalmic Technology Assessments to evaluate new and existing procedures, drugs, and diagnostic and screening tests. The goal of an Ophthalmic Technology Assessment is to review the available research for clinical efficacy, effectiveness, and safety. After review by members of the Ophthalmic Technology Assessment Committee, other Academy committees, relevant subspecialty societies, and legal counsel, assessments are submitted to the Academy’s Board of Trustees for consideration as official Academy statements. The purpose of this assessment by the Ophthalmic Technology Assessment Committee Pediatric Ophthalmology/Strabismus Panel was to review the published literature on the efficacy and safety of laser refractive surgery to treat amblyopia in children.

Background

Amblyopia is one of the leading causes of visual impairment, thought to affect approximately 1% to 5% of children.¹ Amblyopia can be due to a variety of causes, including strabismus and deprivation. However, the most common cause is uncorrected refractive error.² Anisometropic myopia, hyperopia, or astigmatism can result in amblyopia, with a difference in the spherical equivalent as low as 0.50 diopters (D), which puts a child at risk.³ This risk increases with greater magnitudes of difference between eyes.^3,4 Although less common, isoametropic, or bilateral high refractive errors, can also cause amblyopia.³ Traditional treatment options for amblyopia include glasses for correction of refractive error and patching, or atropine of the contralateral eye to promote the use of the amblyopic eye.⁵ Glasses alone can improve visual acuity in at least two-thirds of children⁶ and can be supplemented by patching 1, 2, or 6 hours per day or by atropine 2 to 7 times per week based on the severity of amblyopia.^7,8 Newer therapies being explored include dichoptic binocular therapy,⁹ liquid crystal display glasses,¹⁰ and pharmacologic therapies like levodopa.¹¹

Despite studies demonstrating the success of traditional amblyopia therapy, several challenges limit successful treatment for anisometropic refractive error. One issue is that the asymmetric refractive power of the lens may result in aniseikonia (> 3%) and may be poorly tolerated.¹² Even symmetric high refractive errors may result in visual distortions, particularly when viewing outside of the central visual axis due to the prismatic effect induced by the lens. High minus lenses may also cause minification that limits the potential best-corrected visual acuity (BCVA).¹³ In addition to the optical issues, adherence to treatment is an important factor in managing amblyopia. A child may find glasses uncomfortable to wear, particularly for asymmetric or bilaterally high refractive errors. In anisometropic cases, the child does not perceive the benefit of a treatment since the contralateral eye often sees well without correction. Children with craniofacial abnormalities may not be able to obtain an adequate fit, and those with neurodevelopmental or sensory disorders may not be able to tolerate glasses. Other potential concerns include poor cosmesis and interference with sports and activities. Contact lenses are difficult to fit, insert, and remove. Foreign body sensation may limit tolerance, and there is the potential for corneal infection, particularly in children who may lack good hand hygiene and compliance with an effective contact lens care regimen. Finally, expenses associated with glasses and purchasing and updating contact lenses carry a financial burden.

Because of these challenges, laser refractive surgery has been proposed as an alternative to traditional amblyopia therapies that use refractive correction with glasses or contact lenses. Since the introduction of laser refractive surgery and approval by the Food and Drug Administration over 25 years ago for adult populations, there has been substantial technological progress. Several approaches have been developed, including photorefractive keratectomy (PRK), laser epithelial keratomileusis (LASEK), and LASIK; they are all equally effective in addressing myopia, although less so for astigmatism and hyperopia.¹⁴ Although this technology is utilized in adults,¹⁵ there are challenges of incorporating it into the pediatric population. Some of the limitations in children include procedural logistics such as the need for general anesthesia, complications of the procedure itself related to flap dislocation or corneal haze, an unpredictable healing response in the pediatric population, and an unclear refractive stability over time. Additionally, refractive surgery does not eliminate the need for correction of residual refractive error with glasses or contact lenses, particularly for high refractive errors, or the need for continued amblyopia therapy because both residual refractive error and amblyopia requiring treatment may be present after refractive surgery. As a result, laser refractive surgery has been largely limited to off-label use in cases when a child is unable to tolerate or has failed traditional methods using glasses or contact lenses.

Questions for Assessment

The focus of this assessment is to address the following question: What is the safety and effectiveness of laser refractive surgery to treat amblyogenic anisometropic refractive error in children 18 years of age and younger?

Description of Evidence

A literature search was conducted in October 2021 in the PubMed database with no date restrictions and limited to articles published in English. The search strategy used the following terms: ((refractive surgery[Title] OR (refractive[Title] AND surgery[Title]))) AND (amblyopia[ti] OR amblyopic[ti]) (Keratectomy[tiab] OR photorefractive keratectomy[tiab] OR PRK[tiab] OR subepithelial keratectomy [tiab] OR laser in situ keratomileusis[tiab] OR refractive surgery[tiab] OR corneal refractive surgery[tiab] OR Laser-assisted in situ keratomileusis[tiab] OR LASIK[tiab] OR Laser epithelial keratomileusis[tiab] OR LASEK) OR ((excimer[tiab] OR excimer laser[tiab]) AND (surgery[tiab] OR refractive surgery[tiab])) AND amblyopia[mh] OR amblyopia[tw] OR amblyopic[tw] (((keratectomy/methods [MeSH terms]) OR (keratomileusis, laser in situ/methods [MeSH terms])) OR (lasers, excimer/therapeutic use[MeSH terms])) AND (amblyopia[MeSH terms] OR amblyopia[text word] OR amblyopic[text word]).

The search identified 137 potentially relevant abstracts, which were reviewed by the first author (KMC), and 69 were selected for full-text review. Those that met the following inclusion criteria were included in the final assessment: (1) the research was original; (2) the primary objective of the study was to evaluate the safety and vision outcomes in eyes that have undergone laser refractive surgery to address amblyogenic anisometropia; (3) the study reported at least one of the following outcomes: spherical equivalent, mean of the absolute value of prediction errors, the proportion of eyes within 1.0 D of predicted, the proportion of eyes with a myopic/hyperopic or astigmatism outcome compared with predicted, or amblyopia treatment effectiveness; (4) the study included at least 3 months of follow-up; (5) at least 10 eyes were included in the series; (6) the study included a statistical analysis of results; and (7) the study included children 18 years of age or younger.

After full-text review, 11 articles were deemed to have met the inclusion criteria specified above. The panel methodologist (RHT) then assigned a level of evidence to each study using the American Academy of Ophthalmology’s guidelines that are based on the rating scale developed by the Oxford Centre for Evidence-Based Medicine.¹⁶ A level I rating was assigned to well-designed and well-conducted randomized controlled trials and systematic reviews. A level II rating was assigned to well-designed cohort studies and nonrandomized controlled cohort/follow-up trials. A level III rating was assigned to case-series or to lower-quality case-control or cohort studies.

Published Results

The published studies varied significantly regarding patient inclusion criteria, demographics, design, analysis, and outcomes. Of the 11 studies, one was a case-control study¹⁷ and the remainder were case series.^18–27 The 11 studies included in this assessment are summarized in Table 1.

Table 1.

Summary of Included Studies

Author, Year	No. Patients Treated (no. eyes if different)	Mean Age in Years (range)	Refractive Error (no. patients)	Laser Procedure (no. patients)	Preoperative BCVA	BCVA at Study Endpoint	Preoperative Spherical Equivalent	Postoperative Spherical Equivalent at Study Endpoint	Mean Follow-up Duration (range)	Success within 1 D of Target (% eyes)	Complications (no.)
Agarwal et al, 200025	16	8.4 ± 1.83 years (range, 5–11 years)	Myopia	LASIK	0.53 ± 0.28 (range, 0.17–1.00)	0.54 ± 0.27 (range, 0.17–1.00)	−14.88 ± 3.69 D (range, −9.00 to −23.00 D)	−1.44 ± 0.14 D (range, 0 to −2.50 D)	1 year (no range)	43.7%	Free flap (2); grade 2 corneal haze (3)
Autrata et al, 200417	27	5.4 ± 2.1 years (range, 4–7 years)	Myopia	PRK (13), LASEK (14)	0.23 ± 0.21	0.78 ± 0.19	−8.25 ± 2.37 D (range, −6.00 to −11.25 D)	−1.48 ± 1.13 D (range, +0.75 to −2.25 D)	2 years (no range)	53%	Corneal haze (4)–not visually significant
Ghanem et al, 201019	18	6.7 ± 3.4 years (range, 4–9 years)	Myopia	LASIK	0.26 ± 0.21	0.82 ± 0.17	−9.25 ± 3.43 D (range, −6 to −12.75 D)	−1.50 ± 1.23 D (range, +1.0 to −3.5 D)	2 years (no range)	55.6%	None
Kulikova et al, 202020	24	8.0 ± 2.10 years (range, 5–15 years)	Hyperopia	LASIK	0.23 ± 0.18	0.54 ± 0.27	+4.51 ± 1.69 D (range, +0.75 to +8.38)	−0.11 ± 1.48 D (range, −3.50 to +3.00 D)	7 years (range, 6.9–7.4 years)	38%	None
Lin et al, 200921	24	7.4 ± 1.9 years (range, 5–14 years)	Mixed: myopia (19) and hyperopia (5)	LASIK	0.76 ± 0.43 logMAR	0.31 ± 0.38 logMAR	Myopic: −8.01 ± 2.70 D (range, −15.00 to 3.00 D) Hyperopic: +7.40 ± 1.73 D (range, +5.25 to +9.75 D)	Myopic: −1.32 ± 2.47 D (range, −6.00 to +1.25 D) Hyperopic: +3.15 ± 0.86 D (range, +2.25 to +4.13 D)	33.3 ± 14.2 months (range, 18.5–74.2 months)	50%	Focal opacity at edge of flap (1)
Ram et al, 201926	8 (12)	5.7 years (range, 3–9 years)	Mixed: myopia (7) and hyperopia (1)	PRK	0.99 logMAR	0.628 logMAR	Myopic: −10.26 D (range, −6.25 to −13.00) Hyperopic: +5.62 D (range, +5.25 to +6.00 D)	Myopic: −2.75 D (range, −8.38 to +1.25 D) Hyperop»c: +2.50 D (range, +2.50 to +2.50)	6.5 ± 1.26 years (range, 5–9 years)	N/A	None
Samir et al, 202118	124	7.41 ± 1.3 years (range, 4.62–10.94 years)	Myopia	ReLEX/SMILE	0.31 ± 0.10 logMAR	0.48 ± 0.16 logMAR	−7.07 ± 1.45 (range, −10.63 to −4.50 D)	−0.86 ± 0.68 D	4 years	89%	Radial tear at incision site (2); lenticule decentration (5)
Tychsen et al, 200527	35 (36)	8.4 years (range, 4–16 years)	Mixed: myopia (34) and hyperopia (1)	PRK (18), LASEK (17)	20/87 (range, 20/40 to fix and follow)	0.49 ± 0.34 logMAR (range, 20/20 to fix and follow)	Myopic: −11.48 D (range, −3.25 to −24.25 D) Hyperopic: +5.87 (no range)	Myopic: Mean N/A. (range, −11.50 to +1.25 D). mean of correction 8.95 ± 2.89 D (range, −3.25 ± 15.50 D) Hyperopic: +4.50 D (no range)	29.2 months (range, 4–42 months)	89%	Corneal haze (3)
Utine et al, 200822	32	10.3 ± 3.1 years (range, 4–15 years)	Hyperopia	LASIK	0.20 ± 0.17 (range, 0.01–0.8)	0.35 ± 0.25 (range, 0.1–1.0)	+5.17 ± 1.65 D	+1.39 ± 1.21 D	20.1 ± 15.1 months (range, 12–60 months)	47%	Flap striae (2); Corneal haze (1)
Yin et al, 200723	74	10.2 ± 2.7 years (range, 6–14 years)	Mixed; myopia (32) and hyperopia (42)	LASIK	Myopic: 0.4 ± 0.25 Hyperopic: 0.23 ± 0.21	Myopic: 0.59 ± 0.28 Hyperopic: 0.53 ± 0.31	Myopic: −10.49 ± 4.31 D (range, −17.25 to −4.62 D) Hyperopic: +6.41 ± 1.28 D (range, +4.00 to +9.12 D)	Myopic: −1.63 ± 2 D Hyperopic: +0.6 ± 0.8 D	Mean Myopic: 18.31 months, Hyperopic: 17.45 months (range for both 6–36 months)	N/A	None
Zhang et al, 201724	33	9.04 ± 3.04 years (range, 6–16 years)	Myopia	LASIK (30), ReLEX/SMILE (3)	0.98 ± 0.63 logMAR	0.41 ± 0.33 logMAR	−10.00 ± 2.39 D	−0.60 ± 1.43 D	8.17 ± 3.23 months (range, 6–16 months)	87%*	None

BCVA = best corrected visual acuity; D = diopter; femto-LASIK = femtosecond-assisted (Femto) laser in-situ keratomileusis (LASIK); F/F = fix and follow; LASEK = laser epithelial keratomileusis; LASIK = laser-assisted in situ keratomileusis; N/A = not available or not reported; PRK = photorefractive keratectomy; ReLEX = refractive lenticule extraction; SMILE = small incision lenticule extraction.

^*At 1 month after surgery

Studies Reporting on Myopic Anisometropia

Five studies focused solely on eyes with myopic refractive error. In a comparative case series study by Autrata and Rehurek,¹⁷ 27 children (mean age, 5.4 years; range, 4–7 years) who underwent PRK (13 eyes) or LASEK (14 eyes) for amblyopia due to myopic anisometropia more than 3 D and contact lens intolerance (group A) were compared with a control group of 30 children (mean age, 5.1 years) with no significant differences in the mean age, amount of myopic anisometropia, or amblyopia treatment regimen who underwent treatment with contact lenses and patching (group B). All patients had a 2-year follow-up, and the dominant eye was patched. The mean spherical equivalent in group A was −8.25 ± 2.37 D (range, −6.00 to −11.25 D) preoperatively and −1.48 ± 1.13 D (range, +0.75 to −2.25 D) at the 2-year study end point. No significant complications were reported apart from mild pain and discomfort on the first postoperative day, and 4 patients experienced visually insignificant corneal haze. At 3 months postoperatively, 74% of eyes in group A were within ±1.00 D of target refraction, but this declined to 53% at 2 years. Overall, the mean decimal equivalent BCVA was 0.23 ± 0.21 preoperatively and 0.78 ± 0.19 at 2 years in group A, whereas the mean BCVA in group B was initially 0.16 ± 0.19 and improved to 0.42 ± 0.15. The difference in BCVA was significantly better in group A than group B at the study end point, because there was a gain of 4 to 8 lines for 53% of the children in group A but only 20% in group B. Although there were no statistically significant differences in the initial visual acuity, refractive error, or amblyopia treatment regimen, the authors attributed the better 2-year BCVA in refractive surgery patients to the permanent correction of the anisometropia, reduced spectacle aberration, and improved retinal image quality. The authors concluded that PRK and LASEK were safe and effective in children aged 4 to 7 years who did not tolerate contact lenses and who had better visual outcomes than with standard amblyopia therapy.

A large retrospective study by Samir et al¹⁸ evaluated the effects of femtosecond small incision lenticule extraction in 124 eyes of 124 children with a mean age of 7.41 ± 1.3 years (range, 4.62–10.94 years) who had myopic anisometropia of 6.00 D or more and a cycloplegic spherical equivalent of −10.00 D or less. The mean preoperative spherical equivalent was −7.07 ± 1.45 D, which decreased to −0.28 ± 0.58 D at 3 months and −0.88 ± 0.68 D at 4 years. With success defined as decreasing the anisometropia to 3.00 D or less, 89% (110/124) of eyes had a spherical equivalent within ±1.00 D of the intended correction at 3 months and 75% (18 of 24) at 4 years. There was a myopic shift ranging from 0.28 to 0.88 D over 4 years, which was attributed to increased axial length and the biomechanical and epithelial components of the cornea. The complications noted included 2 cases of mild radial tears at the incision site and 5 cases of lenticule decentration; however, these were mild and had no further consequences beyond the need for glasses. The authors concluded that the procedure improved the visual acuity of amblyopic eyes after 4 years of follow-up with or without maintenance after amblyopia therapy.

In a study by Zhang and Yu,²⁴ 33 amblyopic patients with a mean age of 9.04 ± 3.04 years (range, 6–16 years) with myopic anisometropia of 5.00 D or more who could not tolerate glasses or contact lenses and failed occlusion therapy underwent femto-LASIK (30 eyes) or small incision lenticule extraction (3 eyes). The mean preoperative spherical equivalent was −10.00 ± 2.39 D, which improved to −0.60 ± 1.43 D. The logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.98 ± 0.63 preoperatively to 0.41 ± 0.33 at approximately 8 months after surgery. No patients lost lines of visual acuity, and there were no complications reported. Approximately 87% of patients were within 1 D of goal at 1 month; however, at the mean follow-up of 8.17 ± 3.23 months, there was a myopic shift of −0.35 D in treated eyes. The authors concluded that refractive surgery outcomes were promising but that more patients and longer follow-up are needed.

Ghanem et al¹⁹ studied 18 eyes of 18 children with a mean age of 6.7 ± 3.4 years (range, 4–9 years) with myopic anisometropic amblyopia of 4.00 D or more who failed 6 months of occlusion therapy and subsequently underwent LASIK. The mean spherical equivalent was −9.25 ± 3.43 D (range, −6 to −12.75 D) preoperatively, which improved to −1.50 ± 1.23 D (range, ±1.0 to −3.5 D) postoperatively at 2 years. At 6 months, 14 eyes (77.8%) were within 1 D of a target, defined as emmetropia if the refractive error was present only in the amblyopia eye or the achievement of “balance in refraction” if a refractive error was present in the contralateral eye. The mean decimal equivalent BCVA significantly improved from 0.26 ± 0.21 preoperatively to 0.82 ± 0.17 by 2 years after LASIK. Despite this improvement, the number of eyes at target declined to 10 eyes (55.6%) at the final 2-year follow-up, with a mean regression of −2.25 ± 1.7 D (range, −4.5 to −0.5 D). Although minor pain and discomfort were noted on the first postoperative day, no other complications were noted. The authors concluded that LASIK was safe but that longer follow-up and larger studies are needed. Likewise, Agarwal et al²⁵ studied 16 eyes of 16 children (mean age, 8.4 ± 1.83 years; range, 5–11 years) who underwent LASIK to address myopic anisometropic amblyopia of more than 4.00 D. The mean preoperative spherical equivalent was −14.88 ± 3.69 D (range, −9.00 to −23.00 D), and the mean spherical equivalent was −1.44 ± 1.14 D (range, 0 to −2.50 D) at 12 months after surgery. The authors noted that the postoperative spherical equivalent was −1.00 D or less in 7 of 16 eyes (43.7%). The mean preoperative BCVA in decimal equivalent was 0.53 ± 0.28 (range, 0.17–1.00) and did not differ significantly from the mean postoperative BCVA of 0.54 ± 0.27 (range, 0.17–1.00). Complications included 2 free flaps, only 1 persistent decrease in BCVA by 1 line, and 3 eyes with corneal haze, 2 of which were visually significant and associated with a preoperative refractive error of more than −17.0 D. There were no IOP or retinal complications. The authors did not evaluate regression as an outcome.

Studies Reporting on Mixed Anisometropic Refractive Error and Myopia

Refractive surgery outcomes of the myopic eyes in the 4 studies that included both myopic and hyperopic eyes were analyzed.

In a large study by Yin et al,²³ 32 of the 74 eyes (mean age, 10.2 ± 2.7 years; range, 6–14 years) with myopic anisometropia measuring 4.50 D or more underwent LASIK. The mean preoperative spherical equivalent was −10.49 ± 4.31 D (range, −17.25 to −4.62 D). Although the authors did not include the postoperative spherical equivalent at the last visit, the mean preoperative anisometropic myopia was reduced from −10.13 ± 2.49 D (range, −15.75 to −5.37 D) to −2.20 ± 1.05 D. The decimal equivalent BCVA for distance in the myopic group improved from 0.4 ± 0.25 to 0.59 ± 0.28 at 3 years after surgery. Although 6 eyes had peripheral haze 1 month after surgery, all resolved by 6 months. No other complications were reported. With an average follow-up 18.31 months (range, 6 months to 3 years), no regression was noted at 6 months postoperatively; however, the myopic cohort had a statistically significant regression at 36 months to −1.63 D. The authors concluded that more patients and longer followup were needed to see if the myopic shift was influenced by age and had similarity to regression seen in adults.

A retrospective review by Lin et al²¹ analyzed 24 children with a mean age of 7.4 ± 1.9 years (range, 5–14 years) diagnosed with anisometropia of 3.00 D or more who underwent LASIK. Nineteen of these eyes underwent treatment for myopia with a preoperative myopic spherical equivalent of −8.01 ± 2.70 D (range, −15.00 to −3.00). The spherical equivalent improved to −1.32 ± 2.47 D (range, −6.00 to +1.25 D) postoperatively at a mean follow-up period 33.3 ± 14.2 months (range, 18.5–74.2 months). Of the myopic eyes, 12 of 19 (63.2%) were within 1 D and 14 (73.7%) were within 2 D of the target refraction. Regression was noted in 11 myopes, with a mean of −2.74 ± 2.37 D (range, −6.00 to −0.25 D). Additionally, 7 patients progressed to hyperopia +0.73 ± 0.37 D (range, +0.25 to +1. 25 D). Although the authors indicated the preoperative visual acuity improved from a mean of 0.76 ± 0.43 logMAR to 0.31 ± 0.38 logMAR after surgery, they did not separate the myopic and hyperopic visual outcomes. No complications were reported apart from a focal opacity at the flap edge in 1 patient, which was not visually significant.

Tychsen et al²⁷ assessed 36 eyes of 35 children (mean age 8.4 years; range, 4–16 years) who underwent LASEK (16 patients) or PRK (18 patients). These eyes included 1 hyperopic eye from 1 patient and both eyes of 1 child with bilateral myopia with bilateral ametropia of more than 5.00 D; the more myopic eye with anisometropia greater than 4.00 D was enrolled for the remainder of the patients. Of the 34 myopic eyes, the mean preoperative spherical equivalent was −11.48 D (range, −3.25 to −24.25 D). At a mean follow-up 29.2 months (range, 4–42 months), 89% (31) were corrected to ±1.00 D of goal, defined as matching the refraction in the contralateral eye. The final postoperative refraction ranged from −11.50 to +1.25 D. Regression was demonstrated in 24 of 35 eyes (69%) at a rate of −0.088 ± 0.22 D per month or −1.06 D per year. The regression correlated with the severity of postoperative corneal haze (r = 0.356, P < 0.001) and younger age at surgery (r = 0.395, P < 0.0001), with no difference based on technique. The BCVA improved in 34 (97%) children, but only by 1 line in 13 of 34 (38%) (preoperative range, fix and follow to 20/40; postoperative range, fix and follow to 20/20). In contrast to other studies, corneal haze measured at grade 2 or higher was reported in 22% of patients, although only 3 patients had haze exceeding 2+. There was no relationship between corneal haze and technique. However, the severity of haze showed weak correlation with the amount of laser correction (r = 0.157, P < 0.0001) and younger age at surgery (r = 0.115, P < 0.001).

In a small study by Ram et al,²⁶ 10 myopic eyes (7 patients, 3 bilateral) underwent PRK to treat myopic anisometropia of more than 3.00 D. Similar to the more extensive studies, the mean preoperative spherical equivalent decreased (from −10.26 D to −2.75 D), and the BCVA improved (from 20/200 to 20/80) postoperatively. Although regression was not discussed as an outcome, no patients had corneal haze or corneal ectasia at the final follow-up.

Studies Reporting on Hyperopic Anisometropia

Two studies focused on children with strictly hyperopic anisometropic amblyopia. Utine et al²² reported on 32 children with a mean age of 10.3 ± 3.1 years (range,4–15 years) with hyperopic anisometropia more than 2.00 D who underwent LASIK after completing amblyopia treatment to balance the refractive error between eyes. The mean preoperative refraction was +5.17 ± 1.65 D, which improved to +1.39 ± 1.21 D at a mean follow-up of 20.1 ± 15.1 months (range, 12–60 months). Approximately half of the eyes (47%) were within ±1.00 D. The mean preoperative decimal BCVA was 0.20 ± 0.17 (range, 0.01–0.8) and overall improved to a mean postoperative decimal BCVA of 0.35 ± 0.25 (range, 0.1 −1.0), although visual acuity remained the same in 9 eyes (28.1%). The authors reported complications that included flap striae, which were not visually significant in 2 eyes, and haze in 1 eye, resulting in a loss of 1 line of BCVA. They concluded that LASIK was safe but longer follow-up was needed.

In a study of 24 eyes of 24 patients with hyperopic anisometropia measuring 3.00 D or more and a mean age of 8 ± 2.10 years (range, 5–15 years) who underwent femto-LASIK, Kulikova et al²¹ found that the preoperative cycloplegic refraction improved from +4.51 ± 1.69 D (range, +0.75 to +8.38) to −0.11 ± 1.48 D (range, −3.50 to +3.00 D). Of all the patients, 38% were within 1 D of the plan initially; however, there was a regression of 0.90 ± 1.68 D over the mean follow-up of 7 years (range, 6.9–7.4 years). The mean decimal BCVA preoperatively was reported as 0.23 ± 0.18 (range, 0.03–0.9), which improved to 0.54 ± 0.27 (range, 0.10–1.00) at 7 years postoperatively, improving by 1 to 7 lines. Although no complications were reported, the authors noted that surgically induced astigmatism is a potential factor in the correction of hyperopia and that vector analysis and higher-order aberration analysis should be conducted. The authors concluded that refractive surgery represents a viable treatment strategy for anisometropia when other methods have failed but that more research was needed.

Studies Reporting on Mixed Anisometropic Refractive Error and Hyperopia

Four studies that included both myopic and hyperopic eyes analyzed the outcomes of refractive surgery in hyperopic eyes. The largest number of eyes was in a study by Yin et al,²³ who included 42 eyes of 42 children with hyperopic anisometropia measuring 3.50 D or more. The mean hyperopic spherical equivalent was +6.41 ± 1.28 D (range, +4.00 to +9.12 D) preoperatively. Although the authors did not report the postoperative spherical equivalent, they noted that the hyperopic anisometropia decreased from +6.13 ± 1.62 D to +0.56 ± 0.75 D at 3 years after surgery with an average follow-up 17.45 months (range, 6 months to 3 years). The BCVA at distance improved from 0.23 ± 0.21 to 0.53 ± 0.31 at 3 years after surgery. There was no regression reported in study patients overall or in the hyperopic cohort at 6 months. No other complications were reported.

The 3 other studies included a smaller number of hyperopic eyes, and all noted a reduction in the spherical equivalent postoperatively.^21,26,27 In general, no significant complications were reported; however, regression was noted in 2 of the 3 studies.

Conclusions

The available data from the level III evidence reviewed in this assessment demonstrate that the ability to achieve target refraction within 1 D using laser refractive surgery to address anisometropic amblyogenic refractive error in children are variable, but the magnitude of anisometropia appears to be decreased. Correction or improvement of anisometropia did not necessarily correlate with visual improvement, perhaps because the children were older at the time of refractive surgery and had previously failed traditional amblyopia therapy. Also, regression of the refractive error is a major concern in both myopic and hyperopic patients; therefore, long-term follow-up is needed to better assess outcomes.

All examined studies contained significant differences in methodology, which precludes a direct comparison of the results. These differences included patient demographics such as the age at time of surgery, the severity of amblyopia, and the duration of and adherence to amblyopia therapy. Multiple types of laser refractive surgery techniques were used, even within the same study. Refractive error parameters also ranged drastically in magnitude for both myopia, and hyperopia. Additionally, different outcome measures, including a lack of a standard definition of success, limited comparison. Also, the complications were not uniformly discussed and did not consistently include details about higher-order aberrations, glare, reduced contrast with haze, and decentration. Finally, all studies had small sample sizes with variable durations of follow-up data.

Future Research

Future research on the effectiveness of laser refractive surgery to address amblyogenic refractive error in children 18 years of age and younger requires high-quality, prospective, randomized controlled trials with longer follow-up given the potential for changes in refractive error in children over time. Standardization of patient age strata, timing of refractive surgery with regard to the period of plasticity, the severity of amblyopia, the use and duration of prior amblyopia interventions, the follow-up duration, and the application of standardized definitions for success are all factors that warrant assessment. Additionally, prospective studies that rigorously define refractive targets and compare techniques for laser refractive surgery are essential. The use of newer refractive technologies such as femtosecond laser surgery and small incision lenticule extraction should also be evaluated.

Pictures & Perspectives.

Firecracker Cataract

A healthy 5-year-old boy was brought to our clinic with decreased vision in both eyes (OU). His best-corrected visual acuity was 20/200 OU. Slit-lamp examination revealed developmental cataract OU, in the form of multiple glistening sparks and lines originating from the center of the anterior capsule of lens, resembling a firecracker illuminating the sky (Fig A, B). His family history was unremarkable, and there was no history of trauma. The child underwent sequential cataract aspiration with intraocular lens implantation OU, with postoperative visual acuity of 20/40 OU. Pediatric cataract is a significant cause of childhood blindness worldwide. Early diagnosis and surgical intervention are essential to prevent irreversible loss of vision (Magnified version of Fig A–B is available online at www.aaojournal.org).

Abbreviations and Acronyms:

BCVA

best-corrected visual acuity

D

diopters

LASEK

laser epithelial keratomileusis

LASIK

laser-assisted in situ keratomileusis

logMAR

logarithm of the minimum angle of resolution

PRK

photorefractive keratectomy