Surgical interventions for bilateral congenital cataract in children aged two years and under.

BACKGROUND: Congenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require surgery. Cataracts are proportionally the most treatable cause of visual loss in childhood, and are a particular problem in low-income countries, where early intervention may not be possible. Paediatric cataracts provide different challenges to those in adults. Intense inflammation, amblyopia (vision is obstructed by cataract from birth which prevents normal development of the visual system), posterior capsule opacification and uncertainty about the final trajectory of ocular growth parameters can affect results of treatment. Two options currently considered for children under 2 years of age with bilateral congenital cataracts are: (i) intraocular lens (IOL) implantation; or (ii) leaving a child with primary aphakia (no lens in the eye), necessitating the need for contact lenses or aphakic glasses. Other important considerations regarding surgery include the prevention of visual axis opacification (VAO), glaucoma and the route used to perform lensectomy. OBJECTIVES: To assess the effectiveness of infant cataract surgery or lensectomy to no surgery for bilateral congenital cataracts in children aged 2 years and under. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 1); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 25 January 2022. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared infant cataract surgery or lensectomy to no surgery, in children with bilateral congenital cataracts aged 2 years and younger. This update (of a review published in 2001 and updated in 2006) does not include children over 2 years of age because they have a wider variety of aetiologies, and are therefore managed differently, and have contrasting outcomes. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two review authors extracted data independently. We assessed the risk of bias of included studies using RoB 1 and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified three RCTs that met our inclusion criteria with each trial comparing a different aspect of surgical intervention for this condition. The trials included a total of 79 participants under 2 years of age, were conducted in India and follow-up ranged from 1 to 5 years. Study participants and outcome assessors were not masked in these trials. One study (60 children) compared primary IOL implantation with primary aphakia. The results from this study suggest that there may be little or no difference in visual acuity at 5 years comparing children with pseudophakia (mean logMAR 0.50) and aphakia (mean logMAR 0.59) (mean difference (MD) -0.09 logMAR, 95% confidence intervals (CIs) -0.24 to 0.06; 54 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain as to the effect of IOL implantation compared with aphakia on visual axis opacification (VAO) (risk ratio (RR) 1.29, 95% CI 0.23 to 7.13; 54 participants; very low-certainty evidence). The trial investigators did not report on the cases of amblyopia. There was little evidence of a difference betwen the two groups in cases of glaucoma at 5 years follow-up (RR 0.86, 95% CI 0.24 to 3.10; 54 participants; very low-certainty evidence). Cases of retinal detachment and reoperation rates were not reported. The impact of IOL implantation on adverse effects is very uncertain because of the sparse data available: of the children who were pseudophakic, 1/29  needed a trabeculectomy and 8/29 developed posterior synechiae. In comparison, no trabeculectomies were needed in the aphakic group and 2/25 children had posterior synechiae (54 participants; very low-certainty evidence).  The second study (14 eyes of 7 children under 2 years of age) compared posterior optic capture of IOL without vitrectomy versus endocapsular implantations with anterior vitrectomy (commonly called 'in-the-bag surgery'). The authors did not report on visual acuity, amblyopia, glaucoma and reoperation rate. They had no cases of VAO in either group. The evidence is very uncertain as to the effect of in-the-bag implantation in children aged under 1 year. There was a higher incidence of inflammatory sequelae: 4/7 in-the-bag implantation eyes and 1/7 in optic capture eyes (P = 0.04, 7 participants; very low-certainty evidence). We graded the certainty of evidence as low or very low for imprecision in all outcomes because their statistical analysis reported that a sample size of 13 was needed in each group to achieve a power of 80%, whereas their subset of children under the age of 1 year had only 7 eyes in each group. The third study (24 eyes of 12 children) compared a transcorneal versus pars plana route using a 25-gauge transconjunctival sutureless vitrectomy system. The evidence is very uncertain as to the effect of the route chosen on the incidence of VAO, with no cases reported at 1 year follow-up in either group. The investigators did not report on visual acuity, amblyopia, glaucoma, retinal detachment and reoperation rate. The pars plana route had the adverse effects of posterior capsule rupture in 2/12 eyes, and 1/12 eyes needing sutures. Conversely, 1/12 eyes operated on by the transcorneal route needed sutures. We graded the outcomes with very low-certainty because of the small sample size and the absence of a priori sample size calculation. AUTHORS' CONCLUSIONS: There is no high level evidence for the effectiveness of one type of surgery for bilateral congenital cataracts over another, or whether surgery itself is better than primary aphakia. Further RCTs are required to inform modern practice about concerns, including the timing of surgery, age at which surgery should be undertaken, age for implantation of an IOL and development of complications, such as reoperations, glaucoma and retinal detachment. Standardising the methods used to measure visual function, along with objective monitoring of compliance with the use of aphakic glasses/contact lenses would greatly improve the quality of study data and enable more reliable interpretation of outcomes.

Differential Experience-Dependent Plasticity of Form and Motion Mechanisms in Anisometropic Amblyopia.

Purpose: We measure neural responses associated with form and motion processing in children with anisometropia before and after treatment with spectacles and occlusion. Methods: In this prospective, case-control treatment study, 10 children with anisometropia and amblyopia and 16 age-matched visually normal children participated. Steady-state visual evoked potentials (VEP) were recorded from electrodes over the occipital cortex. The visual stimulus comprised a horizontal bar grating into which Vernier offsets were introduced and withdrawn periodically at 3.75 Hz. The VEP amplitude at 3.75 Hz (first harmonic [1F]) and 7.5 Hz (second harmonic [2F]) were recorded to index the sensitivity of form/position-sensitive versus motion/transient-sensitive neural populations, respectively. Response amplitude at 1F and 2F were recorded over a series of 10 logarithmically spaced offset sizes before and after treatment. Main outcome measures are VEP amplitude versus displacement functions, interocular response amplitude differences. Results: After relaxing into spectacles (minimally-treated state), form/position-sensitive responses in the dominant/less ametropic eye of the children with anisometropia were larger and responses in the more ametropic eye were smaller than those of controls. Motion-transient responses were equal to those of controls in the less ametropic eye, but were smaller than controls in the more ametropic eye. After treatment, responses did not differ from those of controls. Conclusions: Form and motion responses are differentially susceptible to neural deprivation via optical blur. Form responses are more plastic than motion responses in minimally-treated children with anisometropic amblyopia. Most treatment effects occurred above threshold range, suggesting some treatment effects are not detected clinically.

Crowded letter and crowded picture logMAR acuity in children with amblyopia: a quantitative comparison.

AIMS: Clinically, picture acuity tests are thought to overestimate visual acuity (VA) compared with letter tests, but this has not been systematically investigated in children with amblyopia. This study compared VA measurements with the LogMAR Crowded Kay Picture test to the LogMAR Crowded Keeler Letter acuity test in a group of young children with amblyopia. METHODS: 58 children (34 male) with amblyopia (22 anisometropic, 18 strabismic and 18 with both strabismic/anisometropic amblyopia) aged 4-6 years (mean=68.7, range=48-83 months) underwent VA measurements. VA chart testing order was randomised, but the amblyopic eye was tested before the fellow eye. All participants wore up-to-date refractive correction. RESULTS: The Kay Picture test significantly overestimated VA by 0.098 logMAR (95% limits of agreement (LOA), 0.13) in the amblyopic eye and 0.088 logMAR (95% LOA, 0.13) in the fellow eye, respectively (p<0.001). No interactions were found from occlusion therapy, refractive correction or type of amblyopia on VA results (p>0.23). For both the amblyopic and fellow eyes, Bland-Altman plots demonstrated a systematic and predictable difference between Kay Picture and Keeler Letter charts across the range of acuities tested (Keeler acuity: amblyopic eye 0.75 to -0.05 logMAR; fellow eye 0.45 to -0.15 logMAR). Linear regression analysis (p<0.00001) and also slope values close to one (amblyopic 0.98, fellow 0.86) demonstrate that there is no proportional bias. CONCLUSIONS: The Kay Picture test consistently overestimated VA by approximately 0.10 logMAR when compared with the Keeler Letter test in young children with amblyopia. Due to the predictable difference found between both crowded logMAR acuity tests, it is reasonable to adjust Kay Picture acuity thresholds by +0.10 logMAR to compute expected Keeler Letter acuity scores.

The repeatability of best corrected acuity in normal and amblyopic children 4 to 12 years of age.

PURPOSE: The main purpose of this work was to measure repeatability of line-by-line logMAR (logarithm of the minimum angle of resolution) acuity in normal and amblyopic children, while adequately controlling for optical defocus. METHODS: The Lea Symbols Chart is a constant-crowding, equal-logMAR increment chart similar in design to the Early Treatment Diabetes Retinopathy Study [ETDRS] chart. LogMAR visual acuity was tested twice in each eye of 32 amblyopic and 11 normal children. Each test commenced with screening in which one of the three central symbols was chosen for identification starting with the 1.0- or 0.9-logMAR line, progressing to every second line until incorrect identification occurred. Symbol-by-symbol presentation then commenced at the logMAR line containing the last correctly identified symbol. The threshold was recorded as the last logMAR line where four of four or four of five correct responses occurred (i.e., line-by-line scoring). Retesting by the same examiner was identical and occurred within the same session. RESULTS: There was no significant difference in repeatability among normal, fellow, or amblyopic eyes. The difference between test and retest thresholds lay between +/-0.10 logMAR in 93% of eyes. The 95% limits of agreement for the difference was +/-0.18 logMAR. Repeatability in eyes tested first did not differ from that in those tested second in either the normal or amblyopic groups. CONCLUSIONS: In the age-group tested, the line-by-line method of threshold scoring compares favorably with previous reports of both line-by-line and interpolated threshold scoring. There was no clinically meaningful difference in repeatability between the normal and amblyopic children tested.

Measurement of position acuity in strabismus and amblyopia: specificity of the vernier VEP paradigm.

PURPOSE: An objective measure of positional acuity is desirable in the nonverbal clinical population. This study was conducted to investigate the specificity of the vernier VEP as a measure of positional acuity, evaluating the potential confound of asymmetric motion responses that may be present in some groups of patients. These motion responses could masquerade as position-specific responses, since they occur at the same response frequency as the vernier-related response. METHODS: Twelve observers with early-onset esotropia (EOE), 30 children with untreated amblyopia, and 15 control children underwent swept vernier VEP acuity testing accompanied by a swept motion control stimulus. The control condition was used to detect the presence of artifactual responses not related to position sensitivity. The patients with EOE were selected for high levels of motion asymmetry as documented with oscillating gratings presented monocularly. As a measure of motion confound (penetration), the proportion of first-harmonic responses recorded in the control condition was determined. RESULTS: The penetration rate in the vernier condition in each study group (EOE: 0.93%; amblyopes: 4.26%; normal subjects: 2.40%) and the entire group (2.85%) was acceptably low. The level of penetration was not significantly influenced by the presence of amblyopia. CONCLUSIONS: The vernier VEP paradigm, when applied in the manner described, can be interpreted as a measure of position sensitivity. The presence of motion asymmetry or untreated amblyopia does not affect the validity of vernier measurements made.

Detection of the slipped extraocular muscle after strabismus surgery.

PURPOSE: To estimate the frequency of slipped extraocular muscle (SM) in cases of repeat strabismus surgery and to compare the results of a number of putative preoperative tests for the detection of SM, with direct intraoperative inspection and histologic confirmation. DESIGN: Retrospective analysis of audit records followed by prospective interventional case series. PARTICIPANTS: Case records of 715 adults presenting for repeat surgical correction of horizontal strabismus. Five patients suspected of having horizontal SM were consecutively recruited for the prospective case series. METHODS: Slipped extraocular muscle frequency was determined retrospectively from surgical outcome data in 715 adult horizontal strabismus surgeries in 1 center. A separate prospective study examined 5 participants with putative SM in detail. Gaze-dependent clinical tests (squint magnitude, eye movement range, palpebral fissure widening, naked-eye saccadic velocity estimation, intraocular pressure change) and saccade main sequence parameters (infrared eye-tracking) were recorded before and 2 weeks after corrective surgery. Intraoperative diagnosis was made by direct muscle examination and confirmed by histologic examination. Length of slippage and forced duction tests were intraoperative outcome measures. RESULTS: Slipped extraocular muscle frequency was 10.6%. The muscles of 3 participants in the prospective series were slipped. Direct intraoperative inspection accurately identified all SM cases. All other clinical tests produced false-positive and false-negative results, although SM was suggested preoperatively by limited eye movement range. Distorted saccadic velocity profiles were significantly (P<0.0001) associated with prior strabismus surgery. Saccade main sequence parameters were not diagnostic for SM. CONCLUSIONS: Direct intraoperative inspection can accurately diagnose SM. Preoperative diagnosis of long-standing SM was not possible. In contradiction to a previous report, SM was not reliably associated with reduced peak saccadic velocity. The association between distorted saccadic velocity profiles and previous strabismus surgery is, to our knowledge, reported here for the first time.

The effect of monocularly and binocularly induced astigmatic blur on depth discrimination is orientation dependent.

PURPOSE: Naturally occurring astigmatism varies according to the age of the person. Although uncorrected astigmatism may be associated with meridional amblyopia, there is little information of its effect on stereopsis. The purpose of this study was to determine the effect of astigmatism on depth discrimination and whether this was dependent on the axis of the astigmatism. METHODS: Astigmatic blur was induced in four healthy subjects (mean age, 31.5 years; range, 22 to 42 years) using plain cylinders (-8.75 D to +11.5 D) for orientation control and Jackson cross-cylinders (0 to 12 D) for spherical neutrality. Horizontal, vertical, and oblique astigmatism was induced with five monocular and three binocular axis steps. Depth discrimination was recorded at near using Frisby, TNO, and Titmus stereoacuity tests and at distance (4 m) using the variable distance stereoacuity test. Visual acuity was recorded at 0.4 m and 4 m. RESULTS: Visual acuity and depth discrimination degraded with increasing astigmatic blur. The effect of monocular astigmatic blur on depth discrimination and visual acuity was not dependent on the axis of orientation. For binocular astigmatic blur, the reduction in depth discrimination was dependent on the axis of the induced astigmatism (p < 0.01). The maximum effect occurred with orthogonal-oblique orientations (x45 left; x135 right), followed by against-the-rule (ATR) astigmatism; with-the-rule (WTR) astigmatism had the least effect (p < 0.001). CONCLUSIONS: The lesser effect of WTR compared with ATR astigmatic blur on depth discrimination may reflect the contribution of horizontal compared with nonhorizontal disparity processing in stereopsis. The pronounced effect of oblique astigmatic blur may be because of the effects on horizontal and nonhorizontal disparity and interocular differential image blur.

Combined optical and atropine penalization for the treatment of strabismic and anisometropic amblyopia.

INTRODUCTION: The treatment of amblyopia by occlusion of the fellow eye is beset by problems related to compliance, stigmatization, and regression of visual acuity (VA). Atropine or optical penalization has been used as an alternative treatment for amblyopia and might be synergistic as a combination therapy. Combined optical and atropine penalization treatment (COAT) was therefore assessed in patients with anisometropic and strabismic amblyopia. METHODS: Patients with a hypermetropic refractive error in whom occlusion had failed were prescribed daily atropine 1% and a plano spectacle lens to the fellow eye. Outcome measures included VA (LogMAR units), interocular VA difference, adverse events, and adverse reactions. COAT was continued until VA failed to improve after 2 consecutive visits, and then patients were offered occlusion treatment again. RESULTS: Forty-two patients (mean age, 4.73 yrs) were treated with COAT. Patients had attempted occlusion for a mean period of 36 weeks before commencement of COAT. The mean VA of the amblyopic eyes improved after 10 weeks of COAT, from 0.85 (20/113) to 0.28 (20/37) (P <.001), an overall success (doubling of VA) rate of 76%. There was no significant change in the mean VA of the fellow eye as a result of COAT (P =.13). Twenty-two patients recommenced occlusion after COAT for regression (10), lack of further improvement (2), or parental choice (10). The remaining 20 patients maintained their VA without treatment at 93% of post-COAT levels, at a mean follow-up 6.4 months. Overall regression rate was 36%, adverse reaction rate was 2%, adverse event rate was 21%, and presumed compliance rate was 83%. DISCUSSION: COAT is an effective treatment method when occlusion therapy initially fails. COAT is well tolerated and should be considered as an alternative and/or supportive therapy in the management of amblyopia.