The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of ...diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy.
There is currently no consensus on the treatment strategy. Most patients have a limited life expectancy and for these complex treatments are generally not recommended. However, recent advances in systemic therapy have significantly improved survival of certain patients who may benefit from an aggressive ocular approach that could preserve vision. Although external beam radiation therapy is the most widely used treatment, more advanced forms of radiotherapy that are associated with fewer side effects can be proposed in select cases.
In patients with a shorter life expectancy, systemic therapies such as those targeting oncogenic drivers, or immunotherapy can induce a regression of the choroidal metastases, and may be sufficient to temporarily decrease visual symptoms. However, they often acquire resistance to systemic treatment and ocular relapse usually requires radiotherapy for durable control. Less invasive office-based treatments, such as photodynamic therapy and intravitreal injection of anti-VEGF, may also help to preserve vision while reducing time spent in medical settings for patients in palliative care.
The aim of this review is to summarize the current knowledge on choroidal metastases, with emphasis on the most recent findings in epidemiology, pathogenesis, diagnosis and treatment.
•Choroid is the most common ocular site for metastatic spread, especially for breast and lung cancer.•Enhanced imaging of the choroid allows better understanding and precise diagnosis of choroidal metastases.•In case the primary remains unknown, tumor biopsy may help identify the primary and guide treatment.•To date, fractionated radiotherapy remains the treatment of choice for choroidal metastases.•The place of systemic targeted therapy and “office-based” treatment such as PDT or intravitreal antiVEGF should be considered.
To investigate choriocapillaris (CC) blood flow in unaffected fellow eyes of patients with central serous chorioretinopathy (CSC) using quantitative optical coherence tomography angiography (OCTA) ...analysis.
Case-control study.
Patients with acute, recurrent, or persistent CSC, along with healthy sex- and age-matched subjects, were included. Objective assessment of CC blood flow was performed using OCTA measurements. Total area of flow signal voids was quantified at baseline, 3 months, and 6 months. Active serous retinal detachment (SRD) was considered as a potential source of false-positive flow impairment; affected eyes were therefore excluded at onset and during follow-up, if this finding was unresolved at the time of measurement.
Sixty patients with CSC and 60 control subjects were included in this study. The total average flow signal void area was significantly higher in the unaffected eyes of CSC patients at baseline (2.70 ± 0.53 mm2 vs 2.23 ± 0.43 mm2, P < .001). At 3 months, the total average flow signal void area was greater in the affected eyes of CSC patients with resolved SRD compared with unaffected eyes (3.25 ± 0.77 mm2 vs 2.67 ± 0.68 mm2, P < .001). This total average flow signal void area was larger in unaffected eyes at baseline in recurrent/persistent cases of CSC compared to acute forms (3.74 ± 0.66 mm2 vs 2.93 ± 0.69 mm2, P = .01).
Vascular abnormalities in CSC involve CC hypoperfusion, suggestive of a primary choroidopathy including ischemic processes. These microvascular flow deficits may constitute one of a number of underlying subclinical changes preceding CSC and other pachychoroid spectrum disorders.
Phosphenes are frequently reported by patients irradiated in the head and neck area. The aim of the present study was to characterize and investigate potential mechanisms of proton beam therapy ...(PBT)–induced phosphenes in a large population of patients undergoing PBT for ocular tumors.
Prospective cohort study.
Consecutive patients who underwent PBT in a single center were included. Immediately after the first session, all patients completed a questionnaire collecting information about the presence of phosphenes as well as their color, shape, and duration. Patient, tumor and treatment characteristics (dose volume histograms) were also collected.
Among the 474 patients included, 62.8% reported phosphenes during the first session of PBT. Reported colors were mainly blue-violet (70.5%) and white (14.1%). The prevalence of phosphenes was higher in younger patients (P = .003); other patient or ocular characteristics were not associated with the occurrence of phosphenes. Irradiation of the macula (P < .001) and/or optic disc (P < .001) were significantly associated with the presence of phosphenes, whereas blue-violet color was only associated with young age and irradiation of macular area (P = .04). Pupillary constriction was reported for 57.1% of patients with phosphenes vs 18.5% of patients without (P < .001). Blue-violet phosphenes (P < .001) and irradiation of macula (P = .001) were statistically associated with pupillary constriction.
The present study reported a high rate of phosphenes in patients irradiated by PBT for ocular tumor. Their blue-violet color and their association with a pupillary constriction probably indicates the stimulation of S-cones and retinal ganglion cells that reflects the activation of the afferent visual pathway.
Članak 13. Europske konvencije za zaštitu ljudskih prava i temeljnih sloboda dugo je vremena smatran supsidijarnim u odnosu na članak 6. stavak 1. i na druge članke te Konvencije. Općenito, kad je ...kod dolazilo do kršenja koje normativne mjere Konvencije, smatralo se suvišnim sankcionirati nepoštivanje prava na djelotvorni pravni lijek. U presudiKudlaprotiv Poljskeu kojoj je sud pristao na provjeravanje sankcioniranja za kršenje članka 13 zbog nepostojanja žalbe koja dozvoljava tužitelju da mu se prizna njegovo pravo na suđenje u razumnom roku, stanje prava se izmjenilo. Namjeravamo izložiti 15 – ak godina kasnije jedan argumentirani prikaz te potonje presude. Pokazat će se, posebno, da europski sudac priznaje stvarnu autonomiju prava na djelotvoran pravni lijek. Članak 13. je dugo vremena bio smatran kao neko sporedno pravo, a sad je postao apsolutno pravo u potpunom smislu. Tu novu dimenziju ovog prava treba povezati s pravom na izvršenje odluka u sudskoj praksi Europskog suda za zaštitu ljudskih prava, i to posebice s presudom Hornsby protiv Grčke od 19. ožujka 1997.
Article 13 of the European Convention for the Protection of Human rights and Fundamental Freedoms has for a long time been considered subsidiary in relation to article 6 subsection 1 and to other ...articles in that Convention. In general, when infringement of any normative measures of the Convention occurred, it was considered to be superfluous to sanction disregard of the right to an effective legal remedy. In the judgement of Kudla vs. Poland where the court agreed to verifying sanctions for infringement of article 13 for disregarding the appeal which allowed the claimant recognition of his right to trial within a reasonable timeframe, the status of rights changed. The intention is to 15 years later present an argumented analysis of that particular judgement. It will be shown that the European judge recognised the true autonomous right to an effective legal remedy. Article 13 has long been considered as a secondary right. Now it has become an absolute right in a complete sense. This new dimension of this right should be linked to the right for implementation of judgement in court practice in the European Court for the Protection of Human Rights, in particular in the judgement Hornsby vs. Greece on 19 March 1997.
Članak 13. Europske konvencije za zaštitu ljudskih prava i temeljnih sloboda dugo je vremena smatran supsidijarnim u odnosu na članak 6. stavak 1. i na druge članke te Konvencije. Općenito, kad je ...kod dolazilo do kršenja koje normativne mjere Konvencije, smatralo se suvišnim sankcionirati nepoštivanje prava na djelotvorni pravni lijek. U presudiKudlaprotiv Poljskeu kojoj je sud pristao na provjeravanje sankcioniranja za kršenje članka 13 zbog nepostojanja žalbe koja dozvoljava tužitelju da mu se prizna njegovo pravo na suđenje u razumnom roku, stanje prava se izmjenilo. Namjeravamo izložiti 15 – ak godina kasnije jedan argumentirani prikaz te potonje presude. Pokazat će se, posebno, da europski sudac priznaje stvarnu autonomiju prava na djelotvoran pravni lijek. Članak 13. je dugo vremena bio smatran kao neko sporedno pravo, a sad je postao apsolutno pravo u potpunom smislu. Tu novu dimenziju ovog prava treba povezati s pravom na izvršenje odluka u sudskoj praksi Europskog suda za zaštitu ljudskih prava, i to posebice s presudom Hornsby protiv Grčke od 19. ožujka 1997.
In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione ...redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER glutathione import triggers H2O2-dependent Bip oxidation through Ero1 reductive activation, which inhibits glutathione import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction, and cytosolic glutathione levels increase. Thus, the ER redox poise is tuned by reciprocal control of glutathione import and Ero1 activation. The ER protein-conducting channel is permeable to small molecules, provided the driving force of a concentration gradient.
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•Cytosol-to-ER glutathione transport proceeds via facilitated diffusion through Sec61•Ero1-dependent Bip (Kar2) oxidation inhibits ER-to-cytosol glutathione transport•ER-to-cytosol transport of glutathione and Ero1 activation are reciprocally regulated•Coupling of glutathione transport to Ero1 activation preserves the ER redox poise
Ponsero et al. show that cytosol-to-ER transport of glutathione proceeds via facilitated diffusion through Sec61. Upon import, glutathione activates Ero1 by reduction, causing Bip oxidation and inhibition of glutathione transport. Coupling of glutathione ER import to Ero1 activation provides a basis for glutathione ER redox poise maintenance.
Iron-sulfur (Fe-S) clusters are essential protein cofactors whose biosynthetic defects lead to severe diseases among which is Friedreich's ataxia caused by impaired expression of frataxin (FXN). Fe-S ...clusters are biosynthesized on the scaffold protein ISCU, with cysteine desulfurase NFS1 providing sulfur as persulfide and ferredoxin FDX2 supplying electrons, in a process stimulated by FXN but not clearly understood. Here, we report the breakdown of this process, made possible by removing a zinc ion in ISCU that hinders iron insertion and promotes non-physiological Fe-S cluster synthesis from free sulfide in vitro. By binding zinc-free ISCU, iron drives persulfide uptake from NFS1 and allows persulfide reduction into sulfide by FDX2, thereby coordinating sulfide production with its availability to generate Fe-S clusters. FXN stimulates the whole process by accelerating persulfide transfer. We propose that this reconstitution recapitulates physiological conditions which provides a model for Fe-S cluster biosynthesis, clarifies the roles of FDX2 and FXN and may help develop Friedreich's ataxia therapies.
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