-
Ophthalmic Surgery, Lasers & Imaging... Feb 2021Torpedo maculopathy (TM) is a rare macular lesion involving the retinal pigment epithelium (RPE). This paper describes a retrospective case report of TM. In addition,...
BACKGROUND AND OBJECTIVE
Torpedo maculopathy (TM) is a rare macular lesion involving the retinal pigment epithelium (RPE). This paper describes a retrospective case report of TM. In addition, the authors present a comprehensive systematic review of 110 cases found in the literature.
PATIENTS AND METHODS
A search for the term "torpedo maculopathy" was conducted on PubMed, Embase, and Web of Science databases and yielded 62 relevant studies.
RESULTS
The majority of cases in the literature, including this case, reported an asymptomatic hypopigmented temporal lesion with occasional satellite lesions. Fluorescein angiography generally revealed hypofluorescence, whereas optical coherence tomography demonstrated RPE thinning as well as choroid hyperreflectivity.
CONCLUSIONS
This is the largest systematic review of torpedo maculopathy to date. The authors' findings confirm that it is a benign, nonprogressive, predominantly unilateral temporal lesion thought to arise during macular development. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:78-83.].
Topics: Fluorescein Angiography; Humans; Macular Degeneration; Retinal Diseases; Retinal Pigment Epithelium; Retrospective Studies; Tomography, Optical Coherence
PubMed: 33626168
DOI: 10.3928/23258160-20210201-04 -
BMJ Open Feb 2021To give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD). (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of different regimens of ranibizumab for neovascular age-related macular degeneration: a network meta-analysis of randomised controlled trials.
OBJECTIVE
To give a comprehensive efficacy and safety ranking of different therapeutic regimens of ranibizumab for neovascular age-related macular degeneration (nAMD).
DESIGN
A systematic review and network meta-analysis.
METHODS
The PubMed, Embase, Cochrane Central Register of Controlled Trials, and other clinical trial registries were searched up to 1 October 2019 to identify related randomised controlled trials (RCT) of different regimens of ranibizumab for nAMD. The primary efficacy outcome was the changes of best-corrected visual acuity (BCVA) at 1 year, the primary safety outcome was the incidence of severe ocular adverse events. Secondary outcomes such as changes of central retinal thickness (CRT) were evaluated. We estimated the standardised mean difference (SMD), ORs, 95% CIs, the surface under the cumulative ranking curves and the mean ranks for each outcome using network meta-analyses with random effects by Stata 14.0.
RESULTS
We identified 26 RCTs involving 10 821 patients with nAMD randomly assigned to 21 different therapeutic regimens of ranibizumab or sham treatment. Ranibizumab 0.5 mg (treat and extend, T&E) is most effective in terms of changes of BCVA (letters, SMD=21.41, 95% CI 19.86 to 22.95) and three or more lines of BCVA improvement (OR=2.83, 95% CI 1.27 to 4.38). However, it could not significantly reduce retreatment times compared with monthly injection (SMD=-0.94, 95% CI -2.26 to 0.39). Ranibizumab 0.5 mg (3+pro re nata)+non-steroidal anti-inflammatory drugs (NSAIDs) is most effective in reducing CRT and port delivery system of ranibizumab (100 mg/mL) could reduce the number of retreatment most significantly. All regimes have no more risk of severe ocular complications (including vitreous haemorrhage, rhegmatogenous retinal detachment, endophthalmitis, retinal tear and retinal pigment epithelium tear) or cardiocerebral vascular complications.
CONCLUSIONS
Ranibizumab 0.5 mg (T&E) is most effective in improving the visual outcome. The administration of topical NSAIDs could achieve additional efficacy in CRT reduction and visual improvement. Both interventions had acceptable risks of adverse events.
Topics: Angiogenesis Inhibitors; Bevacizumab; Humans; Intravitreal Injections; Macular Degeneration; Network Meta-Analysis; Ranibizumab; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 33550238
DOI: 10.1136/bmjopen-2020-040906 -
International Ophthalmology Feb 2021To review the basic principles of ultra-widefield fundus autofluorescence (UWF-FAF) and discuss its clinical application for a variety of retinal and choroidal disorders. (Review)
Review
PURPOSE
To review the basic principles of ultra-widefield fundus autofluorescence (UWF-FAF) and discuss its clinical application for a variety of retinal and choroidal disorders.
METHODS
A systematic review of the PubMed database was performed using the search terms "ultra-widefield," "autofluorescence," "retinal disease" and "choroidal disease."
RESULTS
UWF-FAF imaging is a recently developed noninvasive retinal imaging modality with a wide imaging range that can locate peripheral fundus lesions that traditional fundus autofluorescence cannot. Multiple commercially available ultra-widefield imaging systems, including Heidelberg Spectralis and Optomap Ultra-Widefield systems, are available to the clinician. Imaging by UWF-FAF is more comprehensive; it can reflect the content and distribution of the predominant ocular fluorophore in retinal pigment epithelial cells and evaluate the metabolic status of RPE of various retinal and choroidal disorders.
CONCLUSION
UWF-FAF can detect abnormalities that traditional fundus autofluorescence cannot; therefore, it can be used to better elucidate disease pathogenesis, analyze genotype-phenotype correlations, diagnose and monitor disease.
Topics: Fluorescein Angiography; Fundus Oculi; Humans; Optical Imaging; Retina; Retinal Diseases
PubMed: 33040254
DOI: 10.1007/s10792-020-01609-9 -
The British Journal of Ophthalmology Nov 2021Age-related macular disease (AMD) is a major cause of blindness and there is little treatment currently available by which the progress of the basic disorder can be... (Review)
Review
Age-related macular disease (AMD) is a major cause of blindness and there is little treatment currently available by which the progress of the basic disorder can be modulated. Histological and clinical studies show that the major tissues involved are the outer retina, retinal pigment epithelium, Bruch's membrane and choroid. Because of a wide variation of phenotype from one case to another, it has been suggested that accurate phenotyping would be necessary for assessment of the effectiveness of treatment that is tissue-directed. However, based on findings from the study of human donor material and animal models of disease and of cell culture, it is concluded that retinal pigment epithelial dysfunction plays a central role in the disease process in most, if not all, cases of early AMD. The metabolism of phagosomal material, particularly lipids, and energy generation are interdependent, and dysfunction of both appears to be important in the genesis of disease. Evidence exists to suggest that both can be modulated therapeutically. These metabolic functions are amenable to further investigation in both the normal state and in disease. Once fully characterised, it is likely that treatment could be directed towards a limited number of functions in single tissue, thus simplifying treatment strategies.
Topics: Aging; Bruch Membrane; Choroid; Humans; Lipid Metabolism; Macular Degeneration; Retina; Retinal Pigment Epithelium
PubMed: 32950958
DOI: 10.1136/bjophthalmol-2020-317447 -
Journal of Ophthalmology 2020Some reports described a possible ritonavir-related retinal toxicity. The objective of this research was to review and analyze previous studies conducted on ritonavir... (Review)
Review
Some reports described a possible ritonavir-related retinal toxicity. The objective of this research was to review and analyze previous studies conducted on ritonavir administration and retinal impairment in a narrative synthesis. PubMed was used to perform a systematic review of ritonavir effects and retinal damage. All studies up to December 2019 were considered. Seven single cases and one case series, reporting a total of 10 patients affected by retinal changes secondary to long-term ritonavir treatment, were included in the review. Variable degrees of outer retina and retinal pigment epithelium changes were detected in most of the patients, with two patients showing macular telangiectasia, four patients presenting intraretinal crystal deposits, two patients disclosing a bull's eye maculopathy, and two patients revealing midperipheral bone spicule-like pigment changes. In the present study, we hypothesized that the use of ritonavir in life-saving treatments of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia might expose these patients to the risk of developing a retinotoxicity. We aimed to alert ophthalmologists on the importance of recognizing ritonavir-induced retinal impairment in SARS-CoV-2 patients. These findings are the target for personalized medicine.
PubMed: 32908681
DOI: 10.1155/2020/5350494 -
Journal of Clinical Medicine May 2020Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a... (Review)
Review
Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies.
BACKGROUND
Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety.
METHODS
Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy.
RESULTS
Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years' follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials.
CONCLUSIONS
Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs-future real-world data should be focused on SOAE.
PubMed: 32443612
DOI: 10.3390/jcm9051522 -
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 -
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 -
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 -
International Journal of Molecular... Apr 2020The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used.
METHODS
In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a- and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays.
RESULTS
original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave (Hedges' g 1.181 (0.471-1.892), = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 versus in the range of 10) resulted in a significantly increased effect on vision-based behavior as well. The origin of cells mattered as well. A significantly increased effect was found on vision-based behavior when using ARPE-19 and OpRegen RPE.
CONCLUSIONS
This systematic review shows that RPE transplantation in animal models for retinal degeneration significantly increases a- and b- wave amplitudes and improves vision-related behavior. These effects appear to be more pronounced in young animals, when the number of transplanted cells is larger and when ARPE-19 and OpRegen RPE cells are used. We further emphasize that there is an urgent need for improving the reporting and methodological quality of animal experiments, to make such studies more comparable.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Models, Animal; Publication Bias; Retinal Degeneration; Retinal Pigment Epithelium; Treatment Outcome
PubMed: 32295315
DOI: 10.3390/ijms21082719