Effectiveness of optical treatment in amblyopia and validation of measuring spectacle compliance with the ODM.

PURPOSE: The improvement in visual acuity (VA) was determined during optical treatment in children with amblyopia before their participation in a randomised clinical trial comparing the effect of dichoptic video gaming using virtual reality goggles with occlusion therapy. METHODS: Children aged 4-12 years with an interocular VA difference ≥0.20 logMAR and an amblyogenic factor: strabismus <30Δ, ≥1.00 D anisometropia, astigmatism ≥1.50 D and/or hypermetropia ≥1.50 D were eligible for 16 weeks of optical treatment. Children with previous amblyopia treatment were excluded. Compliance with spectacle wear was measured electronically over 1 week using the occlusion dose monitor (ODM). The reliability of these measurements was verified. The main outcome was an increase in amblyopic eye VA from baseline to 16 weeks. RESULTS: Sixty-five children entered the optical treatment period. Mean age was 6.0 ± 2.2 years (range: 4-12 years; IQR 4.5-6.7 years). Amblyopia was caused by anisometropia in 53 (82%) children, strabismus in 6 (9%) and combined mechanism in 6 (9%). After optical treatment, mean VA improved by 0.20 logMAR (SD 0.28; p < 0.001) and 0.07 in the amblyopic and fellow eye, respectively (SD 0.20; p = 0.03). This resulted in 24 children (37%) with an interocular VA difference <0.20 logMAR and in 17% of children with VA at the start of 0.30 logMAR or worse. Poor VA in the amblyopic eye at baseline (p = 0.001) and high anisometropia (p = 0.001) were associated with VA improvement. On average, spectacles were worn 9.7 ± 2.4 h/day (range: 2.3-13.6 h); mean compliance was 73% ± 18% of estimated wake time. Only ambient temperature ≥ 31°C or when spectacles were worn on top of the head prevented a reliable ODM measurement. CONCLUSIONS: VA improved by two lines resulting in more than a third of the children being treated sufficiently with spectacles alone and no longer being classified as amblyopic. The ODM proved to be a reliable method of measuring compliance with spectacle wear.

Supervised dichoptic gaming versus monitored occlusion therapy for childhood amblyopia: Effectiveness and efficiency.

PURPOSE: To compare the effectiveness and efficiency of supervised dichoptic action-videogame play to occlusion therapy in children with amblyopia. METHODS: Newly diagnosed children with amblyopia aged 4-12 years were recruited, excluding strabismus >30PD. After 16 weeks of refractive adaptation children were randomized to gaming 1 h/week supervised by the researcher, or electronically monitored occlusion 2 h/day. The gaming group played a dichoptic action-videogame using virtual reality goggles, which included the task of catching a snowflake presented intermittently to the amblyopic eye. Contrast for the fellow eye was self-adjusted until 2 identical images were perceived. The primary outcome was visual acuity (VA) change from baseline to 24 weeks. RESULTS: We recruited 96 children, 29 declined and 2 were excluded for language or legal issues. After refractive adaptation, 24 of the remaining 65 no longer met the inclusion criteria for amblyopia, and 8 dropped out. Of 16 children treated with gaming, 7 (6.7 years) completed treatment, whereas 9 younger children (5.3 years) did not. Of 17 treated with occlusion, 14 (5.1 years) completed treatment and 3 (4.5 years) did not. Of 5 children with small-angle strabismus, 3 treated with occlusion completed treatment and 2 treated with gaming did not. Median VA improved by 0.30 logMAR (IQR 0.20-0.40) after gaming, 0.20 logMAR (0.00-0.30) after occlusion (p = 0.823). Treatment efficiency was 1.25 logMAR/100 h (range 0.42-2.08) with gaming, 0.08 (-0.19-0.68) with occlusion (p < 0.001). CONCLUSION: Dichoptic gaming seems a viable alternative for older children with refractive amblyopia after glasses adaptation. Treatment efficiency with gaming under continuous supervision was 15 times higher than with occlusion at home.

Eye colour and skin pigmentation as significant factors for refractive outcome and residual accommodation in hypermetropic children: a randomized clinical trial using cyclopentolate 1% and tropicamide 1.

PURPOSE: To compare the refractive outcome and residual accommodation with respect to various degrees of iris and skin pigmentation in hypermetropic children using 2 drops of cyclopentolate 1% (C + C) or 1 drop of cyclopentolate 1% and 1 drop of tropicamide 1% (C + T). METHODS: Two hundred fifty-one hypermetropic children were classified according to iris and skin pigmentation (light, medium, dark) and received randomized and double-blind C + C or C + T. Refractive error (spherical equivalent, SEQ) was determined using the Retinomax-K + 3. In 204 subjects, residual accommodation (RA) was determined using the PlusoptiX PowerRefractor. RESULTS: A linear mixed model with a light-irided and light skin-pigmented reference group receiving C + T (mean SEQ +3.10 ± 1.87D) indicated significant less hypermetropia in subjects with a dark iris having a medium- and dark-pigmented skin in C + T, -1.02 ± 0.29 (-1.59/-0.45) and -1.53 ± 0.30 (-2.10/-0.95); and in subjects having a light-, medium- and dark-pigmented skin in C + C, -0.74 ± 0.34 (-1.41/-0.06), -1.26 ± 0.30 (-1.85/-0.66) and -1.84 ± 0.30 (-2.42/-1.26). Similar findings were present for RA. Our model with a light-irided and light skin-pigmented reference group receiving C + T (mean RA +0.84 ± 0.61D) indicated significantly higher RA in dark-irided subjects with medium- and dark-pigmented skin in C + T, +1.05 ± 0.19 (+0.67/+1.43) and +1.35 ± 0.20 (+0.9/+1.74), and in C + C, +1.13 ± 0.21 (+0.71/+1.55) and +1.90 ± 0.19 (+1.51/+2.28). CONCLUSIONS: We found solid evidence that skin pigmentation rather than iris pigmentation is the decisive factor for effectiveness of cycloplegics. Awareness of the limitations of cycloplegic regimens in dark-irided/pigmented children is needed. Our study showed that cyclopentolate 1% combined with tropicamide 1% provides more accurate refractive outcomes both statistically and clinically integrating the factor skin pigmentation for dark-irided subjects.

A randomized clinical trial using atropine, cyclopentolate, and tropicamide to compare refractive outcome in hypermetropic children with a dark iris; skin pigmentation and crying as significant factors for hypermetropic outcome.

Purpose: To evaluate the refractive outcome and influencing factors following atropine 0.5% eye-drops applied twice daily during 2 ½ days at home and two drops of cyclopentolate 1% (C+C) and one drop of cyclopentolate 1% and one drop of tropicamide 1% (C+T) applied in an outpatient clinic, in hypermetropic children with a dark iris. Methods: Double-blind randomized study including 67 3-6-year-old children receiving C+C in one eye and C+T in the other eye. Two weeks later followed by atropine 0.5% in both eyes. Primary outcome measures were: spherical equivalent (SEQ) following C+C, C+T and atropine, and secondarily SEQ with respect to sex, ethnicity, skin pigmentation (light, medium, dark) and crying. Data on atropine are divided in those with C+C (CC) or C+T (CT) as a first intervention. Results: Mean SEQ±SD for C+C, C+T, atropine-(CC) and atropine-(CT) was +1.74 ± 1.35, +1.77 ± 1.34, +2.15 ± 1.43 and +2.10 ± 1.38 diopter (D). Atropine 0.5% revealed significantly more hypermetropia than C+C and C+T; +0.41 ± 0.43, 95%CI +0.31 to +0.52D and +0.33 ± 0.39, 95%CI +0.24 to +0.34D. No significant difference was present between C+C and C+T; -0.03 ± 0.56, 95%CI -0.16 to +0.11D. Ethnicity and skin-color were strongly associated (r = 0.84, p < .001). Sex was not affecting outcomes (p = .101). Ethnicity was borderline significant (p = .049). Skin-color was a highly significant factor (p = .002). A statistical model combining intervention and skin-color, with light-pigmented subjects receiving atropine-(CC) as reference group (mean SEQ +2.61 ± 1.46D), indicated borderline significantly less hypermetropia in atropine-(CC)-dark: mean decrease (95%CI): -0.81 (-1.66 to +0.05)D and atropine-(CT)-dark -0.87 (-1.70 to -0.03)D, furthermore significantly less hypermetropia in C+C-dark: -1.15 (-1.97 to -0.32)D; C+T-dark: -1.21 (-2.03 to -0.39)D, C+C-medium: -1.02 (-1.81 to -0.24)D and C+T-medium: -0.86 (-1.64 to -0.08)D. Adding crying to the model significantly less hypermetropia was found for subjects crying in all interventions; -0.53 (-0.98 to -0.09)D. Within the interventions, with light-pigmented non-crying subjects as reference group (mean SEQ in atropine, C+C, respectively, C+T: +2.62 ± 1.41, +2.33 ± 1.20 and +2.32 ± 1.20D), showed significantly less hypermetropia in dark-pigmented crying subjects in each individual intervention: atropine -1.10 (-2.01 to -0.19), C+C -1.28 (-2.14 to -0.42) and C+T -1.34 (-2.20 to -0.48)D. For medium pigmented crying subjects this was present in atropine: -0.82 (-1.61 to -0.03)D and C+C: -0.86 (-1.68 to -0.04)D, but not in C+T: -0.58 (-1.25 to +0.09)D. Conclusions: Atropine 0.5% revealed a slight significantly higher hypermetropia. A dark-pigmented skin, especially when crying upon application, resulted in lower hypermetropia in all interventions. C+T provided clinically better results in medium pigmented crying subjects compared to C+C, and equal results compared to atropine 0.5%.

Refractive adaptation and efficacy of occlusion therapy in untreated amblyopic patients aged 12 to 40 years.

PURPOSE: Since neurophysiological and clinical trials have shown evidence for plasticity in the adult visual system, the upper age limit for amblyopia treatment is not rigid. The aim of this study was to investigate the efficacy of occlusion therapy and refractive adaptation in untreated amblyopic patients 12 to 40 years of age. METHODS: In a prospective study, all patients had full orthoptic and ophthalmic assessment including cycloplegic retinoscopy. Patients with a newly prescribed optical correction underwent an 18-week refractive adaptation. All patients were treated with occlusion for 3 h a day for 18 weeks. Acuity gain and responder rates (≥ 0.2 log units) were calculated. The rate of recurrence (visual acuity 9 months after end of the occlusion therapy; ≥ 0.2 log units) and the acuity gain after refractive adaptation were determined. Self-reported compliance to occlusion therapy was assessed. RESULTS: Median age of patients (n = 24) was 32.4 years (IQR 19.2). Best corrected visual acuity at start of occlusion therapy was 0.35 logMAR (IQR 0.5) and 0.30 (IQR 0.4) logMAR at the end of occlusion therapy, an acuity gain of 0.05 logMAR (P = 0.004). Six (25%) patients had an acuity gain of at least 0.2 logMAR units. Reading acuity was improved from 0.4 logMAR (IQR 0.4) to 0.3 logMAR (IQR 0.4) (P = 0.004). Visual acuity was stable 9 months after occlusion therapy. The acuity gain after 18 weeks of refractive adaptation was 0.05 logMAR (P = 0.238, n = 8). Acuity gain by correcting refractive errors was 0.25 logMAR (P = 0.006). Twenty-one (92%) of 24 patients achieved full recording in the calendar. Overall compliance was 17% (IQR 38). Only 5 out of 22 (23%) had acceptable compliance (≥ 50%) to occlusion therapy. Improvement of visual acuity was significantly better in patients with at least 50% compliance (P = 0.013). Compliance was worse in non-native patients than in native patients (P = 0.022). CONCLUSIONS: In adulthood, compliance to occlusion therapy is even more challenging than in children. Noncompliance is the main reason for treatment failure. Only a few patients with acceptable compliance to occlusion therapy had a small but significant improvement of visual acuity. The results suggest that some adults with amblyopia retain a degree of cortical plasticity. We found that untreated adult amblyopic patients did not wear optical correction on the amblyopic eye. The highest treatment benefit was achieved by correcting refractive errors prior to following period of refractive adaptation.

Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2.

PURPOSE: To compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. SETTING: Twelve European study centers. DESIGN: Randomized clinical trial. METHODS: Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. RESULTS: The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 µm and 9.7 µm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P = .007 and P = .014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. CONCLUSIONS: Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect.

European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 1.

PURPOSE: To compare the efficacy of a topical nonsteroidal antiinflammatory drug, topical corticosteroid, and a combination of both drugs to prevent the occurrence of cystoid macular edema (CME) after cataract surgery in nondiabetic patients. SETTING: Twelve European study centers. DESIGN: Randomized clinical trial. METHODS: Nondiabetic patients having uneventful cataract surgery were included in this study. Patients were randomized to receive topical bromfenac 0.09% twice daily for 2 weeks or dexamethasone 0.1% 4 times daily with 1 drop less per day every following week, or a combination of both. The primary outcome was the difference in central subfield mean macular thickness 6 weeks postoperatively. Secondary outcome measures included corrected distance visual acuity as well as the incidence of CME and clinically significant macular edema (CSME) within 6 weeks and 12 weeks postoperatively. RESULTS: This study comprised 914 patients. Six weeks postoperatively, the central subfield mean macular thickness was 288.3 µm, 296.0 µm, and 284.5 µm in the bromfenac group, dexamethasone group, and combination treatment group, respectively (overall P = .006). The incidence of clinically significant macular edema within 12 weeks postoperatively was 3.6%, 5.1%, and 1.5%, respectively (overall P = .043). CONCLUSION: Patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% had a lower risk for developing CSME after cataract surgery than patients treated with a single drug.

Adverse reactions following routine anticholinergic eye drops in a paediatric population: an observational cohort study.

OBJECTIVES: To investigate the presence, nature and relationship to age, sex, ethnicity and body mass index (BMI) of adverse reactions following routine cycloplegic eye drops in children. DESIGN: Prospective observational cohort study. SETTING: Ophthalmology outpatient clinic Dutch metropolitan hospital; February, March and April 2009. PARTICIPANTS: Children aged 3-14-year-old children receiving two drops of cyclopentolate 1% (C+C) or one drop of cyclopentolate 1% and one drop of tropicamide 1% (C+T). Patients were categorised by age (3-6, 7-10 and 11-14 years), sex, ethnicity and body mass index (BMI) (low, normal or high). OUTCOME MEASURES: Rate and nature of adverse reactions reported at 45 min following treatment. Crude and adjusted ORs for reporting an adverse reaction using stepwise regression analysis with BMI, age, ethnicity and sex. RESULTS: 912 of 915 eligible patients participated (99.7%). Adverse reactions were reported for C+C in 10.3% and in C+T in 4.8% (42/408 and 24/504, p=0.002), respectively. Central effects were present in 95% in C+C and in 92% in C+T. Compared to C+T, an increased risk was present in C+C (crude OR 2.3 (1.4 to 3.9), p=0.002). Forward adjustment showed BMI to be an influencing factor in treatment (OR 3.1 (1.7 to 5.6), p<0.001). In a multivariate model, a dose of cyclopentolate remained associated with adverse reactions. Analysis per BMI and regime and age category and regime, indicated associations with low BMI (OR C+C 21.4 (6.7 to 67.96), p<0.001, respectively, C+T 5.2 (2.1 to 12.8), p<0.001) and young age (OR C+C 8.1 (2.7 to 24.8), p<0.001). CONCLUSIONS: Adverse reactions were common and almost exclusively involved the central nervous system. Both presence and severity were associated with repeated instillation of cyclopentolate 1%, low BMI and young age. In specific paediatric populations, a single dose of cyclopentolate must be considered. Vital function monitoring facilities are advisable. Adjustment of guidelines is recommended.

Comparison of wavefront-guided photorefractive keratectomy and foldable iris-fixated phakic intraocular lens implantation for low to moderate myopia.

PURPOSE: To compare and evaluate the visual and refractive outcomes of myopic wavefront-guided photorefractive keratectomy (PRK) and foldable phakic intraocular lens (pIOL) implantation for myopia. SETTING: Department of Ophthalmology, Haaglanden Medical Center, The Hague, The Netherlands. DESIGN: Comparative case series. METHODS: The differences in visual acuity and residual refractive outcomes after wavefront-guided PRK and Artiflex foldable pIOL implantation were compared in eyes with low to moderate myopia (spherical error -4.0 to -7.0 diopters [D]; maximum cylinder 2.25 D). One-year follow-up results are presented. RESULTS: At 1 year postoperatively, the mean decimal Snellen uncorrected distance visual acuity was 1.05 ± 0.21 (SD) in the PRK group (60 eyes) and 1.04 ± 0.21 in the pIOL group (33 eyes) and the mean corrected distance visual acuity (CDVA), 1.21 ± 0.18 and 1.24 ± 0.13, respectively. In the PRK group, 21.7% of eyes lost 1 to 3 lines of CDVA and 11.7% of eyes gained 1 or 2 lines. In the pIOL group, no eye lost lines of CDVA and 42% gained 1 or 2 lines. At 1 year, 80.0% of eyes in the PRK group and 90.9% of eyes in the pIOL group were within ± 0.50 D of the spherical equivalent. CONCLUSION: There were no statistically significant differences in safety and efficacy between the pIOL group and the PRK group at 1 year. However, the percentage of eyes that gained lines of CDVA was significantly higher in the pIOL group.

Visual evoked potentials during suppression in exotropic and esotropic strabismics: strabismic suppression objectified.

BACKGROUND: We performed an electrophysiological study in order to objectify suppression in strabismus. The extent of cortical involvement in the process of interocular suppression was also explored. Possible differences in the suppressive process of esotropic and exotropic strabismics were also studied. METHODS: An electroencephalographic recorder with eight leads was applied to the posterior one-third of the skull; three occipital, three parietal, and two temporal leads. We measured the activity of these visual cortical areas during stimulation of each eye under monocular as well as binocular viewing conditions with hemisinusoidal light pulses in a nature-like complex visual background. Recordings were made from six primary esotropic strabismic subjects and four primary exotropic and one consecutive exotropic strabismic subject. Also, five normal controls were studied. RESULTS: A characteristic, triphasic response complex was found at approximately 80 ms following the start of each light pulse under monocular viewing conditions in the dominant and the nondominant eye. However, under dichoptic viewing conditions in the nondominant eye of all esotropic cases as well as in the nondominant eye of three of five exotropic cases, this response complex was completely absent. They showed approximately 100% reduction of their cortical response activity. CONCLUSIONS: These results show the vast extent of the cortex that is involved in the suppressive process, giving a good insight in the power of suppression.