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Ophthalmology. Retina Aug 2020To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM). (Meta-Analysis)
Meta-Analysis
PURPOSE
To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM).
CLINICAL RELEVANCE
A sensitive and reliable anatomic measure to monitor disease progression is needed in treatment trials for CHM. However, the long-term natural history of the residual retinal pigment epithelium (RPE) is unclear, with reported RPE area decline rates varying widely among patients.
METHODS
We searched in 7 literature databases up through July 17, 2019, to identify studies that assessed the residual RPE area in untreated eyes with CHM using fundus autofluorescence (FAF). We sought individual-eye data and investigated the RPE decline pattern using 3 models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and log-transformed area of RPE change linearly with time, respectively. To account for different eyes' entry times into the studies, we added a horizontal translation factor to each dataset. The RPE decline rate was estimated using a 2-stage random-effects meta-analysis. We assessed the risk of bias using the Quality In Prognosis Studies tool.
RESULTS
Of 807 articles screened, we included 9 articles containing cross-sectional data (257 eyes) from 6 studies and longitudinal data (229 visits from 68 eyes) from 5 studies. The residual RPE area followed a trend of exponential decay as a function of patient age. After the introduction of horizontal translation factors to longitudinal datasets of individual eyes, the datasets fit along a straight line in the AEM over nearly 60 years (r = 0.997). The decline rate of log-transformed RPE area was 0.050 (95% confidence interval, 0.046-0.055) log(mm)/year and was independent of the baseline RPE area (r = -0.18; P = 0.15) and age (r = 0.06; P = 0.63). In contrast, the decline rates of the area and effective radius of residual RPE strongly correlated with the baseline RPE area (r = 0.90 and 0.61, respectively; P < 0.001).
CONCLUSIONS
The loss of residual RPE area in untreated eyes with CHM follows the AEM over approximately 60 years. Log-transformed residual RPE area measured by FAF can serve as an anatomic endpoint to monitor CHM.
Topics: Atrophy; Choroideremia; Disease Progression; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Retinal Pigment Epithelium; Time Factors; Tomography, Optical Coherence; Visual Acuity
PubMed: 32362554
DOI: 10.1016/j.oret.2020.03.003 -
Ophthalmology. Retina Sep 2020Determining the natural history of unifocal versus multifocal geographic atrophy (GA) secondary to nonexudative age-related macular degeneration. (Meta-Analysis)
Meta-Analysis
TOPIC
Determining the natural history of unifocal versus multifocal geographic atrophy (GA) secondary to nonexudative age-related macular degeneration.
CLINICAL RELEVANCE
The association between GA focality (i.e., unifocal vs. multifocal lesions) and enlargement rate is inconsistent in the literature. Some studies report a comparable growth rate between unifocal and multifocal GA, whereas others suggest the growth rate varies widely between the 2 groups.
METHODS
We searched 5 literature databases up to May 3, 2019, for studies that classified treatment-naïve GA patients based on lesion focality. We performed a random effects meta-analysis to determine the growth rates of GA. To account for different entry times among cohorts, we introduced a horizontal translation factor to the dataset of each cohort. Heterogeneity and study quality were assessed using the I statistic and Quality in Prognosis Studies tool, respectively. Publication bias was evaluated by funnel plots and the Egger test.
RESULTS
We included 12 studies with 3489 eyes from 3001 patients. After the introduction of translation factors, the effective radius of unifocal and multifocal GA enlarged linearly over approximately 7 years. The effective radius growth rate of multifocal GA (0.199±0.012 mm/year) was 46.3% higher than the growth rate of unifocal GA (0.136±0.008 mm/year; P < 0.001). Interestingly, unifocal and multifocal GA lesions with the same total baseline area grew at vastly different rates, with an estimated ratio of the growth rate as 1.46 (between 2 and 3). This difference disappeared after we accounted for different baseline total perimeters between unifocal and multifocal groups. The measured GA growth rate was consistent across studies using color fundus photography, fundus autofluorescence, or OCT (P = 0.35-0.99).
CONCLUSIONS
The effective radius of GA enlarges linearly and steadily over time in both unifocal and multifocal GA. The lesion focality is a significant prognostic factor for the GA effective radius growth rate. We propose that the growth rate of GA area is directly proportional to the total lesion perimeter (a measure of the number of retinal pigment epithelium cells exposed at the lesion border). Additional studies are needed to understand the cellular mechanisms underlying this relationship.
Topics: Fluorescein Angiography; Fundus Oculi; Geographic Atrophy; Humans; Macular Degeneration; Prognosis; Retinal Pigment Epithelium; Tomography, Optical Coherence; Visual Acuity
PubMed: 32423772
DOI: 10.1016/j.oret.2020.03.020 -
Photodermatology, Photoimmunology &... Sep 2020Skin is the organ most extensively exposed to light of a broad range of wavelengths. Several studies have reported that skin expresses photoreceptive molecules called...
BACKGROUND
Skin is the organ most extensively exposed to light of a broad range of wavelengths. Several studies have reported that skin expresses photoreceptive molecules called opsins. However, the identity and functional role of opsins in the human skin remain elusive. We aim to summarize current scientific evidence on the types of opsins expressed in the skin and their biological functions.
METHODS
A primary literature search was conducted using PubMed to identify articles on dermal opsins found in nonhuman animals and humans.
RESULTS
Twenty-two articles, representing, however, a non-exhaustive selection of the scientific papers published in this specific field, met the inclusion criteria. In nonhuman animals, opsins and opsin-like structures have been detected in the skin of fruit fly, zebrafish, frog, octopus, sea urchin, hogfish, and mouse, and they mediate skin color change, light avoidance, shadow reflex, and circadian photoentrainment. In humans, opsins are present in various skin cell types, including keratinocytes, melanocytes, dermal fibroblasts, and hair follicle cells. They have been shown to mediate wound healing, melanogenesis, hair growth, and skin photoaging.
CONCLUSION
Dermal opsins have been identified across many nonhuman animals and humans. Current evidence suggests that opsins have biological significance beyond light reception. In nonhuman animals, opsins are involved in behaviors that are critical for survival. In humans, opsins are involved in various functions of the skin although the underlying molecular mechanisms remain unclear. Future investigation on elucidating the mechanism of dermal opsins will be crucial to expand the therapeutic benefits of photobiomodulation for various skin disorders.
Topics: Animals; Humans; Opsins; Skin
PubMed: 32431001
DOI: 10.1111/phpp.12578 -
Retina (Philadelphia, Pa.) Apr 2022Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden...
PURPOSE
Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment.
METHODS
Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible.
RESULTS
Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status.
CONCLUSION
To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.
Topics: Angiogenesis Inhibitors; Humans; Intravitreal Injections; Macular Degeneration; Ranibizumab; Subretinal Fluid; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Wet Macular Degeneration
PubMed: 34393212
DOI: 10.1097/IAE.0000000000003283 -
BMC Ophthalmology Apr 2024The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels. (Meta-Analysis)
Meta-Analysis
PURPOSE
The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels.
APPROACH
We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions.
RESULTS
A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels.
CONCLUSION
This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.
Topics: Humans; Alleles; Codon, Nonsense; Nerve Tissue Proteins; Genetic Association Studies; Retina; Phenotype; Mutation; Eye Proteins; Pedigree; DNA Mutational Analysis; Membrane Proteins
PubMed: 38622537
DOI: 10.1186/s12886-024-03419-4 -
Ophthalmology May 2020To summarize the rates of atrophy, risk factors, and atrophy-associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received...
TOPIC
To summarize the rates of atrophy, risk factors, and atrophy-associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (VEGF) treatment for macular neovascularization (MNV).
CLINICAL RELEVANCE
Age-related macular degeneration is a leading cause of vision loss worldwide, and VEGF inhibitors are the primary treatment for nAMD. However, atrophy is observed frequently in eyes treated with anti-VEGF therapy, prompting questions regarding a causative role for these therapies in atrophy development.
METHODS
PubMed was searched for articles published in the past 5 years (January 1, 2014, through January 10, 2019). Studies including atrophy outcome(s) in patients with age-related macular degeneration who received anti-VEGF treatment were included. Review articles, retrospective studies, case reports or studies, preclinical studies, prevalence data reports, and non-English studies were excluded. Randomization was not required.
RESULTS
Overall, 145 studies were identified; 29 publications were included, with cohorts ranging from 8 to 1185 eyes. Imaging methods used to assess atrophy varied across studies. All studies confirmed the occurrence of atrophy, and when available, longitudinal data from the included studies demonstrated an increase in atrophy incidence over time. Key risk factors or phenotypes associated with atrophy were fellow eye atrophy, reticular pseudodrusen, increased injections, and type 3 lesion. In addition, visual acuity loss was noted with foveal atrophy.
DISCUSSION
All studies demonstrated that atrophy occurs in the context of MNV treated with anti-VEGF therapy; however, it is not clear whether anti-VEGF treatment is causative of atrophy versus being associated with atrophy development. The included studies were not designed or powered to assess atrophy as a primary outcome. In addition, it is difficult to determine whether prognostic factors directly affect atrophy. Furthermore, patient populations in clinical trials do not necessarily represent real-world patients. Although phenotypes and risk factors may help to identify those at greater risk of atrophy developing, it is important to recognize that adequately treating exudative MNV remains the best option to optimize vision outcomes in patients with nAMD, particularly given the risk of vision loss with undertreatment observed in the real world.
Topics: Angiogenesis Inhibitors; Atrophy; Choroidal Neovascularization; Humans; Intravitreal Injections; Photoreceptor Cells, Vertebrate; Randomized Controlled Trials as Topic; Retinal Pigment Epithelium; Retrospective Studies; Risk Factors; Vascular Endothelial Growth Factor A; Wet Macular Degeneration
PubMed: 32081493
DOI: 10.1016/j.ophtha.2019.11.010 -
The Cochrane Database of Systematic... Mar 2019Rhegmatogenous retinal detachment (RRD) is a separation of neurosensory retina from the underlying retinal pigment epithelium. It is caused by retinal tears, which let... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rhegmatogenous retinal detachment (RRD) is a separation of neurosensory retina from the underlying retinal pigment epithelium. It is caused by retinal tears, which let fluid pass from the vitreous cavity to the subretinal space. Pars plana vitrectomy (PPV), scleral buckling surgery and pneumatic retinopexy are three accepted management strategies whose efficacy remains controversial. Pneumatic retinopexy is considered in a separate Cochrane Review.
OBJECTIVES
The primary objective of this review was to assess the efficacy of PPV versus scleral buckling for the treatment of simple RRD (primary RRD of any extension with up to two clock hours large break(s) regardless of their anterior/posterior localisation) in people with (phakia) or without (aphakia) a natural lens in the eye, or with an artificial lens (pseudophakia). A secondary objective was to assess any data on economic and quality-of-life measures.
SEARCH METHODS
We searched CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; MEDLINE; Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 5 December 2018.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing PPV versus scleral buckling surgery with at least three months of follow-up.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. Two review authors independently extracted the data and study characteristics from the studies identified as eligible after initial screening. We considered the following outcomes: primary retinal reattachment, postoperative visual acuity, final anatomical success, recurrence of retinal detachment, number of interventions needed to achieve final anatomical success, quality of life and adverse effects. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
This review included 10 RCTs (1307 eyes of 1307 participants) from Europe, India, Iran, Japan and Mexico, which compared PPV and scleral buckling for RRD repair. Two of these 10 studies compared PPV combined with scleral buckling with scleral buckling alone (54 participants). All studies were high or unclear risk of bias on at least one domain. Five studies were funded by non-commercial sources, while the other five studies did not report source of funding.There was little or no difference in the proportion of participants who achieved retinal reattachment at least 3 months after the operation in the PPV group compared to those in the scleral buckling group (risk ratio (RR) 1.07, 95% confidence intervals (CI) 0.98 to 1.16; 9 RCTs, 1261 participants, low-certainty evidence). Approximately 67 in every 100 people treated with scleral buckling had retinal reattachment by 3 to 12 months. Treatment with PPV may result in 4 more people with retinal reattachment in every 100 people treated (95% confidence interval (CI) 2 fewer to 11 more).There was no evidence of any important difference in postoperative visual acuity between participants in the PPV group compared to those in the scleral buckling group (mean difference (MD) 0.00 logMAR, 95% CI -0.09 to 0.10, 6 RCTs, 1138 participants, low-certainty evidence).There was little or no difference in final anatomical success between participants in the PPV group and scleral buckling group (RR 1.01, 95% CI 0.99 to 1.04, 9 RCTs, 1235 participants, low-certainty evidence). There were 94 out of 100 people treated with control (scleral buckling) that achieved final anatomical success compared to 96 out of 100 in the PPV group.Retinal redetachment was reported in fewer participants in the PPV group compared to the scleral buckling group (RR 0.75 (95% CI 0.59 to 0.96, 9 RCTs, 1320 participants, low-certainty evidence). Approximately 28 in every 100 people treated with scleral buckling had retinal detachment by 3 to 36 months. Treatment with PPV may result in seven fewer people with retinal detachment in every 100 people treated (95% CI 1 to 11 fewer).Participants treated with PPV on average needed fewer interventions to achieve final anatomical success but the difference was small and data were skewed (MD -0.20, 95% CI -0.34 to -0.06, 2 RCTs, 682 participants, very low-certainty evidence).Very low-certainty evidence on quality of life suggested that more people in the PPV group were "satisfied with vision" compared with the scleral buckling group (RR 6.22, 95% CI 0.88 to 44.09, 1 RCT, 32 participants).All included studies reported adverse effects, however, it was not always clear whether they were reported as number of participants or number of adverse effects. Cataract development or progression was more prevalent in the PPV group (RR 1.71, 95% CI 1.45 to 2.01), choroidal detachment was more prevalent in the scleral buckling group (RR 0.19, 95% CI 0.06 to 0.65) and new/iatrogenic breaks were observed only in the PPV group (RR 8.21, 95% CI 1.91 to 35.21). Estimates of the relative frequency of other adverse effects, including postoperative proliferative vitreoretinopathy, postoperative increase in intraocular pressure, development of cystoid macular oedema, macular pucker and strabismus were imprecise. Evidence for adverse effects was low-certainty evidence.
AUTHORS' CONCLUSIONS
Low- or very low-certainty evidence indicates that there may be little or no difference between PPV and scleral buckling in terms of primary success rate, visual acuity gain and final anatomical success in treating primary RRD. Low-certainty evidence suggests that there may be less retinal redetachment in the PPV group. Some adverse events appeared to be more common in the PPV group, such as cataract progression and new iatrogenic breaks, whereas others were more commonly seen in the scleral buckling group such as choroidal detachment.
Topics: Humans; Postoperative Complications; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Retinal Detachment; Retinal Perforations; Scleral Buckling; Treatment Outcome; Visual Acuity; Vitrectomy
PubMed: 30848830
DOI: 10.1002/14651858.CD009562.pub2 -
Advances in Therapy Jul 2019Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina...
Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina practice and the management and eventual outcome of nAMD. Recent research has focused on evaluating and comparing the efficacy of the two most widely employed anti-VEGF agents, bevacizumab and ranibizumab; however, a subgroup of patients with nAMD demonstrates a suboptimal response to standard therapy. We have therefore conducted a review of pertinent studies published until August 2018 which have documented the clinical efficacy when switching to a different anti-VEGF. Evidence on baseline disease characteristics, injection frequency and disease outcome has been obtained for patients treated with ranibizumab 0.5 mg and/or bevacizumab 1.25 mg and were switched to aflibercept 2 mg. Our review identified 45 studies investigating switching to aflibercept. Our review showed a clear anatomical benefit after the switch in terms of central retinal thickness and pigment epithelium detachment characteristics, whereas the functional outcomes were variable. Remarkable heterogeneity was documented among the relevant studies with regard to several factors including the baseline characteristics of the cohorts, the non-response definition and previous treatment protocols. Larger prospective trials with appropriate control arms are therefore required to elucidate the potential benefit when switching between anti-VEGF agents in refractory nAMD.
Topics: Aged; Angiogenesis Inhibitors; Bevacizumab; Drug Substitution; Humans; Macular Degeneration; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Treatment Outcome
PubMed: 31102206
DOI: 10.1007/s12325-019-00971-0