Central serous chorioretinopathy is a common idiopathic retinal disease characterized by central vision loss from serous detachment of the neurosensory retina, serous pigment epithelial detachments, ...and leakage of fluid through the retinal pigment epithelium into the subretinal space. The concept of an association between exogenous glucocorticoid use and central serous chorioretinopathy is widely accepted among ophthalmologists. Here, we review the evidence for and against such an association. This evidence includes 2 large, case-control studies that found strong associations, and a smaller, population-based study that found no association. We conclude that the preponderance of the literature on this topic supports the existence of an association. Both exogenous and endogenous glucocorticoids have been implicated. Although a mechanism and a causal relationship remain to be established, the association deserves broader recognition among physicians who prescribe glucocorticoids.
To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin).
Experimental animal study.
Twenty Dutch-belted rabbits.
One eye of each of 20 rabbits was injected with 1.25 mg of ...intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum.
Bevacizumab concentrations in the aqueous, vitreous, and serum.
Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10 microg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 microg/ml 3 days after drug administration. A maximum serum concentration of 3.3 mug/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 microg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks.
The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab (Avastin), using the same rabbit model.
...Experimental animal study.
Twenty-eight Dutch-belted rabbits.
One eye of each of 20 rabbits was injected with 0.5 mg of intravitreal ranibizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Ranibizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. A further 8 rabbits were used to measure serum and fellow ranibizumab at additional time points of 3 and 8 hours.
Ranibizumab concentrations in the aqueous, vitreous, and serum.
Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 microg/ml ranibizumab were maintained in the vitreous humor for 29 days. Ranibizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 17.9 microg/ml, 3 days after drug administration. Elimination of ranibizumab from the aqueous humor paralleled that found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab was detected in the serum or the fellow eye.
In the rabbit, the vitreous half-life of 0.5-mg intravitreal ranibizumab is 2.88 days, shorter than the half-life of 1.25-mg intravitreal bevacizumab of 4.32 days. No ranibizumab was detected in the serum or the fellow uninjected eye; whereas small amounts of intravitreal bevacizumab have been detected in the serum and fellow uninjected eye.
To evaluate clinical comorbidities and steroid use as risk factors for central serous retinopathy (CSR).
Using national insurance databases, we conducted a case-control study of beneficiaries with an ...incident diagnosis of CSR between 2007 and 2015 (n=35 492) and randomly selected controls matched on age-based and sex-based propensity scores (n=1 77 460).
The mean age (SD) of cases was 49.1 (12.2) years, and the majority (69.2%) were male. Cases were more likely to have received steroids in the past year (OR 1.14, 95% CI 1.09 to 1.19, p<0.001) and to have comorbid Cushing's syndrome (OR 2.19, 95% CI 1.33 to 3.59, p=0.002), age-related macular degeneration (OR 5.24, 95% CI 5.00 to 5.49, p<0.001), diabetic macular oedema (OR 2.05, 95% CI 1.71 to 2.47, p<0.001) and diabetes mellitus (OR 1.44, 95% CI 1.33 to 1.56, p<0.001). Glaucoma was associated with lower odds of CSR (OR 0.54, 95% CI 0.51 to 0.56, p<0.001). Patients with other previously hypothesised risk factors (including essential hypertension, pregnancy, other autoimmune disease, sleep disorders,
infection and gastro-oesophageal reflux disease) had lower odds of CSR.
Male middle-aged patients with recent steroid exposure were significantly more likely to develop CSR. Other risk factors include diabetes mellitus, diabetic macular oedema and age-related macular degeneration. Other previously hypothesised risk factors did not appear to confer increased risk. More research is needed to confirm and examine underlying pathophysiology.
Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration (wAMD). Many receptor tyrosine ...kinases (RTKs) including vascular endothelial growth factor receptors (VEGFRs) contribute to angiogenesis, whereas the RTK TIE2 is important for vascular stability. Pan-VEGFR tyrosine kinase inhibitors (TKIs) such as vorolanib, sunitinib, and axitinib are of therapeutic interest over current antibody treatments that target only one or two ligands. This study compared the anti-angiogenic potential of these TKIs. A kinase HotSpotTM assay was conducted to identify TKIs inhibiting RTKs associated with angiogenesis and vascular stability. Half-maximal inhibitory concentration (IC.sub.50) for VEGFRs and TIE2 was determined for each TKI. In vitro angiogenesis inhibition was investigated using a human umbilical vein endothelial cell sprouting assay, and in vivo angiogenesis was studied using the chorioallantoic membrane assay. Melanin binding was assessed using a melanin-binding assay. Computer modeling was conducted to understand the TIE2-axitinib complex as well as interactions between vorolanib and VEGFRs. Vorolanib, sunitinib, and axitinib inhibited RTKs of interest in angiogenesis and exhibited pan-VEGFR inhibition. HotSpotTM assay and TIE2 IC.sub.50 values showed that only axitinib potently inhibited TIE2 (up to 89%). All three TKIs effectively inhibited angiogenesis in vitro. In vivo, TKIs were more effective at inhibiting VEGF-induced angiogenesis than the anti-VEGF antibody bevacizumab. Of the three TKIs, only sunitinib bound melanin. TKIs differ in their classification and binding to VEGFRs, which is important because type II inhibitors have greater selectivity than type I TKIs. Vorolanib, sunitinib, and axitinib exhibited pan-VEGFR inhibition and inhibited RTKs associated with pathological angiogenesis. Of the three TKIs, only axitinib potently inhibited TIE2 which is an undesired trait as TIE2 is essential for vascular stability. The findings support the use of vorolanib for therapeutic inhibition of angiogenesis observed in DR, DME, and wAMD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetic retinopathy (DR) is a microvascular disease caused by poorly controlled blood glucose, and it is a leading cause of vision loss in people with diabetes. In this review we discuss the current ...management of DR with particular focus on the use of intraocular anti-vascular endothelial growth factor (anti-VEGF) agents. Intraocular anti-VEGF agents were first studied in the 1990s, and now several of these agents are either FDA approved or used off-label as first-line treatments for DR. Recent evidence shows that anti-VEGF agents can halt the progression of markers of DR severity, reduce the risk of DR worsening, and reduce the onset of new macular edema. These significant benefits have been demonstrated in patients with proliferative DR and the milder nonproliferative DR (NPDR). A wealth of evidence from recent trials and meta-analyses has detailed the intraoperative and postoperative benefits of adjunctive anti-VEGF therapy prior to pars plana vitrectomy (PPV) for proliferative DR with vitreous hemorrhage. In this review, we also discuss literature comparing various anti-VEGF injection regimens including monthly, quarterly, as-needed, and treat and extend protocols. Combination protocols with panretinal photocoagulation (PRP) or PPV are also discussed. Current evidence suggests that anti-VEGF therapies are effective therapy for NPDR and PDR and may also provide significant benefits when used adjunctively with other DR treatment modalities such as PRP or PPV.
To identify the microvascular changes associated with paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) and to improve our understanding of the relevant involvement ...of the three retinal capillary plexuses using projection-resolved optical coherence tomography angiography (PR-OCTA).
This was a retrospective study of 18 eyes with AMN or PAMM imaged with OCTA. We used cross-sectional PR-OCTA to localize reduced flow signal to the superficial (SCP), middle (MCP), or deep capillary plexus (DCP) or choriocapillaris that corresponded to inner retinal PAMM or outer retinal AMN lesions on OCT.
Five eyes with AMN showed outer retinal disruption on OCT associated with reduced DCP flow signal. All three eyes with AMN and follow-up had recovery of DCP flow. Thirteen eyes with PAMM showed middle retinal disruption on OCT associated with reduced flow signal in both the MCP and DCP. Of these, five also had reduced flow signal in the SCP. All 10 eyes with PAMM and follow-up showed variable recovery of flow signal in one or more plexuses. PAMM reperfusion was primarily arterial in nature. Three eyes with PAMM and no evidence of MCP reperfusion experienced severe thinning of the inner nuclear layer (INL), while seven eyes with robust MCP flow signal recovery showed relative preservation of INL thickness.
Using PR-OCTA, we found that AMN was associated with reduced DCP flow signal, while PAMM was associated with reduced MCP and DCP flow signal and occasionally the SCP. The MCP appears to be important in sustaining INL thickness in these eyes.
To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN).
Literature searches of the PubMed and Cochrane Library databases ...were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective.
Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear.
Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.
To characterize preinjection intraocular pressure (IOP) in eyes receiving monthly ranibizumab versus sham or verteporfin photodynamic therapy (PDT) for age-related macular degeneration (AMD).
Post ...hoc analysis of IOP data from 2 phase 3 clinical trials, the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial.
All safety-evaluable patients who received 1 or more injections of sham or PDT or of ranibizumab and had 1 or more postbaseline IOP measurements recorded for the study eye.
Preinjection IOP measurements for study eyes (n = 1125) and fellow eyes in MARINA and ANCHOR at baseline and at each monthly visit through month 24 were analyzed.
End points evaluated were maximum preinjection IOP during the 24-month treatment period; any occurrence of absolute preinjection IOP of 21 mmHg or more, 25 mmHg or more, or 30 mmHg or more; any occurrence of IOP increase of 6 mmHg or more, 8 mmHg or more, or 10 mmHg or more from baseline; any combination of IOP increase of 6 mmHg or more or 8 mmHg or more from baseline with concurrent absolute preinjection IOP of 21 mmHg or more or 25 mmHg or more; glaucoma-related adverse events; new glaucoma medications used for 45 days or more; and glaucoma filtration or laser surgeries.
Across treatment groups, 60.1% to 70.9% of study eyes had a maximum preinjection IOP of less than 21 mmHg. Comparing ranibizumab 0.5 mg versus sham or PTD treatment, respectively: 39.9% versus 29.1% and 10.9% versus 5.1% had maximum preinjection IOPs of 21 mmHg or more or 25 mmHg or more, respectively; 44.1% versus 29.9% and 24.2% versus 13.6% had IOP increases from baseline of 6 mmHg or more or 8 mmHg or more, respectively; 26.1% versus 13.6% and 16.8% versus 9.0% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 21 mmHg or more; 9.6% versus 3.7% and 7.5% versus 2.4% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 25 mmHg or more. No differences were observed in fellow eyes.
Most ranibizumab-treated eyes did not experience sustained preinjection IOP of 21 mmHg or more (>2 consecutive visits) over 24 months. When evaluating the combined IOP end point, more ranibizumab-treated eyes had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, with concurrent highest IOPs of 21 mmHg or more and 25 mmHg or more versus sham or PDT. Intraocular pressure should be monitored in eyes receiving ranibizumab.
Purpose: To report the representation of female ophthalmologists receiving private industry funding from 2015 through 2018, and to compare to previously observed trends.
Retrospective, comparative ...trend study
The study population consisted of US ophthalmologists listed in CMS Open Payments Database. Data were reviewed for payments for research, consulting, honoraria, industry grants, faculty and speakers, royalties, and services other than consulting. The primary outcome measure was percentage of female representation compared to male in each sub-category of payment.
The percentage of female, board-certified ophthalmologists who practiced in the United States ranged from 21.3% to 24.1%. The total number of reported ophthalmologists with industry ties ranged from 1629 to 1873, of whom between 17.2% and 19.4% were women. Women received significantly less industry compensation by than men in 2015 (median average $3273 vs $4825, P = .003), 2016 ($3600 vs $4750, P = .023), 2017 ($2493 vs $3500, P = .013), and 2018 ($2000 vs $3000, P = .011). Women remained underrepresented in receiving payments for research (ranging from 5.4% of total paid for research to 8.0%), consulting (11%-17.4%), honoraria (6%-14.9%), industry grants (4%-41.2%), royalties and licenses (0.1%-10.2%), faculty and speakers (11.6%-16.4%), and services other than consulting (8.4%-28.9%). Compared to 2013-2014, an increasing proportion of women received industry payments for consulting (P = .012), honoraria (P = .007), royalties and licenses (P = .019), faculty and speakers (P = .007), and services other than consulting (P = .007).
Female ophthalmologists remain underrepresented in terms of the percentage of women who receive private industry funding and dollar value of the funding.
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