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Mitochondrial DNA A3243G variant-associated retinopathy: a meta-analysis of the clinical course of visual acuity and correlation with systemic manifestations.
Coussa, RG, Sohn, EH, Han, IC, Parikh, S, Traboulsi, EI
Ophthalmic genetics. 2021;(4):420-430
Abstract
PURPOSE The mitochondrial DNA A3243G (m.3243A>G) variant causes a wide spectrum of phenotypes, with pigmentary retinopathy as the most common ocular finding. We undertook this meta-analysis to investigate the clinical course of visual acuity (VA) in patients with m.3243A>G variant and provide key clinical correlations with systemic manifestations. METHODS A PubMed literature search was performed and studies were selected after satisfying pre-set inclusion criteria. Demographic and clinical data, including retinal findings and systemic manifestations were recorded. Cross-sectional and linear regression analyses were used to investigate the relationship between VA and age, as well as between the age at diagnosis of retinopathy and the mean ages at diagnosis of sensorineural hearing loss or diabetes. The age and prevalence of systemic manifestations among patients with and without retinopathy were studied using t-tests and Mann-Whitney U-tests (performed on binarized data). Likelihood ratios were computed. RESULTS The mean VA (average of both eyes) of 90 patients (72.2% female; 65/90) were collected from 18 studies published between 1990 and 2018. The baseline mean age was 45.2 years (range 17 to 92). The mean logMAR VA was 0.10 (- 0.12 to 1.39). There was a statistically significant linear correlation between the logMAR VA and age (p = .008). The VA of patients less than or equal to 50 years of age was significantly better than that of patients older than 50 years (0.06 vs.0.18 logMAR, p = .002). 67 patients (74.4%) showed a characteristic pigmentary retinopathy with a mean age at diagnosis of 47.9 years (17 to 92) and VA of 0.14 logMAR (- 0.12 to 1.24). Age at diagnosis of retinopathy was linearly correlated with age at diagnosis of hearing loss or diabetes (p < .001). Patients with retinopathy were more likely to have hearing loss (83.6% vs. 56.5%, p = .03) or diabetes (56.7% vs. 17.4%, p = .001) than those without retinopathy. Those with both hearing loss and diabetes had an earlier onset of retinopathy than those without (46.4 vs. 60.4 years, p = .01). Patients without both hearing loss and diabetes were 5.3-fold less likely to develop a retinopathy. CONCLUSIONS Patients with m.3243A>G variant pigmentary retinopathy maintain highly functional VA until around the fifth decade of life, after which significant visual decline ensues. Patients without hearing loss and diabetes have a lower likelihood of exhibiting a retinopathy, which tends to appear about one decade after hearing loss and diabetes are diagnosed.
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Efficacy and Treatment Burden of Intravitreal Aflibercept Versus Intravitreal Ranibizumab Treat-and-Extend Regimens at 2 Years: Network Meta-Analysis Incorporating Individual Patient Data Meta-Regression and Matching-Adjusted Indirect Comparison.
Ohji, M, Lanzetta, P, Korobelnik, JF, Wojciechowski, P, Taieb, V, Deschaseaux, C, Janer, D, Tuckmantel, C
Advances in therapy. 2020;(5):2184-2198
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Abstract
PURPOSE To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet age-related macular degeneration (wAMD) at 2 years. METHODS A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials). RESULTS Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (n = 255), while RBZ T&E was assessed in two trials (n = 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: - 2.29 [- 8.10, 3.58]; M2: - 0.55 [- 6.34, 5.29]). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: - 6.12 [- 7.60, - 4.65]; M2: - 5.93 [- 7.42, - 4.45]). Results of the sensitivity analyses were consistent with the main scenarios. CONCLUSION Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden.
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n-3 Fatty Acid Supplementation in Mothers, Preterm Infants, and Term Infants and Childhood Psychomotor and Visual Development: A Systematic Review and Meta-Analysis.
Shulkin, M, Pimpin, L, Bellinger, D, Kranz, S, Fawzi, W, Duggan, C, Mozaffarian, D
The Journal of nutrition. 2018;(3):409-418
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Abstract
BACKGROUND Epidemiologic studies link maternal seafood and n-3 (ω-3) polyunsaturated fatty acid (PUFA) consumption with improved childhood cognitive development; trials show mixed results. OBJECTIVE We investigated effects of n-3 PUFA supplementation on child cognitive and visual outcomes. METHODS We systematically reviewed and meta-analyzed randomized controlled trials of n-3 PUFA supplementation in mothers or infants (age ≤2 y) and evaluated standardized measures of cognitive or visual development up to age 18 y. Of 6286 abstracts and 669 full-text articles, 38 trials with 53 intervention arms were included. Data were extracted independently in duplicate. Findings were pooled using random-effects meta-analysis across supplementation periods (maternal, preterm, term infant); we also explored subgroup analyses stratified by supplementation period. Heterogeneity was explored using I2, stratified analysis, and meta-regression. Cognitive development was assessed by Bayley Scales of Infant Development mental and psychomotor developmental indexes (MDI, PDI) and intelligence quotient (IQ); visual acuity was assessed by electrophysiological or behavioral measures. RESULTS The 38 trials (mothers: n = 13; preterm infants: n = 7; term infants: n = 18) included 5541 participants. When we explored effects during different periods of supplementation, n-3 PUFA supplementation improved MDI in preterm infants (3.33; 95% CI: 0.72, 5.93), without statistically significant effects on PDI or IQ in different intervention period subgroups. Visual acuity [measured as the logarithm of the minimum angle of resolution (logMAR)] was improved by supplementation in preterm (-0.08 logMAR; 95% CI: -0.14, -0.01 logMAR) and term infants (-0.08 logMAR; 95% CI: -0.11, -0.05 logMAR), with a nonsignificant trend for maternal supplementation (-0.02 logMAR; 95% CI: -0.04, 0.00 logMAR). In main analyses pooling all supplementation periods, compared with placebo, n-3 PUFA supplementation improved MDI (n = 21 trials; 0.91; 95% CI: 0.005, 1.81; P = 0.049), PDI (n = 21 trials; 1.06 higher index; 95% CI: 0.10, 2.03; P = 0.031), and visual acuity (n = 24; -0.063 logMAR; 95% CI: -0.084, -0.041 logMAR; P < 0.001) but not IQ (n = 7; 0.20; 95% CI: -1.56, 1.96, P = 0.83), although few studies assessed this endpoint. Potential publication bias was identified for MDI (Eggers P = 0.005), but not other endpoints. Significant differences in findings were not identified by world region, race, maternal education, age at outcome assessment, supplementation duration, DHA or EPA dose, DHA:AA ratio, or study quality score (P-interaction > 0.05 each). CONCLUSIONS n-3 PUFA supplementation improves childhood psychomotor and visual development, without significant effects on global IQ later in childhood, although the latter conclusion is based on fewer studies.