Choroidal neovascularisation complicating geographic atrophy in age-related macular degeneration.

Abstract OBJECTIVE: To investigate the morphological and functional outcomes after intravitreal ranibizumab injections for choroidal neovascularisation (CNV) complicating geographic atrophy (GA). DESIGN: Retrospective, interventional, consecutive case series. METHODS: We reviewed the charts of all consecutive patients with GA due to age-related macular degeneration (AMD), who received intravitreal ranibizumab injections for the development of CNV at least 24 months earlier. RESULTS: 21 treatment-naive eyes of 21 consecutive patients (4 men, 17 women, mean age 86.9±1.6 years) were included. In 95.2% of eyes a type 2 CNV was present, extrafoveal in 42.8% of cases. After a mean of 5.0±0.87 (range 1-20) intravitreal ranibizumab injections, best-corrected visual acuity (BCVA) significantly worsened at the 24-month follow-up visit (0.73±0.05 vs 0.88±0.08 logMAR, respectively; p=0.01). A significant reduction of intraretinal cystic lesions, subretinal fluid and pigment epithelium detachment (p<0.001) and a significant increase of GA area (p=0.003) were present at last visit. CONCLUSIONS: Ranibizumab treatment of GA-associated CNVs provides no BCVA improvement at 24 months follow-up despite an anatomic response of CNV. Low effectiveness of ranibizumab in these cases is likely due to GA progression

Update of intravitreal steroids for the treatment of diabetic macular edema

Diabetic macular edema is considered the most important factor related to visual impairment in patients with diabetic retinopathy. Together with the use of grid and focal laser photocoagulation, today the intravitreal administration of pharmacotherapies represents the standard of care for the treatment of this complication: anti-vascular endothelium growth factor agents and steroids are the drugs currently used for this aim. Differently from laser therapy, which prevents visual deterioration, the intravitreal approach allows the promotion of visual recovery. However, the intravitreal injections require to be repeated with high frequency, and this carries the risk of drug- and procedure-related adverse effects

Intravitreal ranibizumab for choroidal neovascularization in a patient with angioid streaks and multiple evanescent white dots

Background: To report a patient with angioid streaks (ASs) and coincident multiple evanescent white dot syndrome (MEWDS) who developed choroidal neovascularization (CNV). Case presentation: A 20-year-old woman presented with reduced vision (20/100) in her left eye (LE). Based on a complete ophthalmologic examination the patient was diagnosed with ASs and coincident MEWDS. Two weeks later best-corrected visual acuity (BCVA) improved up to 20/25 and the MEWDS findings almost disappeared. Two months later BCVA dropped again (20/100) due to the development of CNV which was treated by a single intravitreal injection of ranibizumab (0.5 mg/0.05 mL). One month after this BCVA improved up to 20/40, and there was regression of the CNV. There was no need for retreatment at the last follow-up visit, 1 year after the ranibizumab injection, when the patient showed further recovery of BCVA up to 20/25. Conclusions: In this case of ASs, MEWDS completely resolved after 2 weeks, but 2 months later CNV developed. A single intravitreal injection of ranibizumab had a long-lasting effect. Larger series are necessary to clarify the pathogenesis of CNV in such cases and the role of intravitreal ranibizumab

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells.

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involvement in promoting proliferation, invasiveness, resistance to apoptosis and stemness. By RT-PCR, methylation-specific PCR, fluorescent in situ hybridization, DNA sequence, western blot and immunofluorescence analyses, we have shown that-in comparison with parental MG63 cells where TP53 gene is hypermethylated, rearranged and in single copy-in 3AB-OS cells, TP53 is unmethylated, rearranged and in multiple copies, and mutp53 (p53-R248W/P72R) is post-translationally modified and with nuclear localization. p53-R248W/P72R-knockdown by short-interfering RNA reduced the growth and replication rate of 3AB-OS cells, markedly increasing cell cycle inhibitor levels and sensitized 3AB-OS cells to TRAIL-induced apoptosis by DR5 up-regulation; moreover, it strongly decreased the levels of stemness and invasiveness genes. We have also found that the ectopic expression of p53-R248W/P72R in MG63 cells promoted cancer stem-like features, as high proliferation rate, sphere formation, clonogenic growth, high migration and invasive ability; furthermore, it strongly increased the levels of stemness proteins. Overall, the findings suggest the involvement of p53-R248W/P72R at the origin of the aberrant characters of the 3AB-OS cells with the hypothesis that its GOF can be at the root of the dedifferentiation of MG63 cells into CSCs

Spontaneous traumatic macular hole closure in a 50-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Traumatic macular holes (TMH) are well-known complications of ocular contusion injury. Spontaneous closure occurs in approximately 50% of cases, but rarely after the age of thirty. We report a case of spontaneous closure of a full thickness macular hole due to a blunt trauma and we suggest possible mechanisms for this closure.</p> <p>Case presentation</p> <p>A 50-year-old Greek woman was referred with a history of reduced best-corrected visual acuity after blunt trauma to her right eye. Diagnosis was based on fundoscopic, optical coherence tomography as well as fluorescein angiography findings with follow-up visits at two days, 20 days and five months. Fundoscopy revealed a full-thickness TMH with a minor sub-retinal hemorrhage and posterior vitreous detachment. The presence of a coagulum in the TMH base was observed. Subsequently, TMH closure was observed.</p> <p>Conclusion</p> <p>The clot in the TMH base, potentially a hemorrhage by-product containing a significant quantity of platelets, may have simulated the clot observed after autologous serum use, thus facilitating a similar effect. This may have stimulated glial cell migration and proliferation, thus contributing to spontaneous hole closure.</p

Comparison of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness Values Using Spectral-Domain and Swept-Source OCT

PURPOSE: To compare peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness measurements obtained with spectral domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) using an OCT-angiography scanning protocol, and their ability to distinguish among patients with glaucoma, glaucoma suspects (GS), and healthy controls (HC). METHODS: Cross-sectional study of 196 eyes (81 glaucoma, 48 GS, and 67 HC) of 119 participants. Participants underwent peripapillary and macular OCT with SD-OCT and SS-OCT. Parameters of interest were average and sector-wise pRNFL and mGCIPL thickness. Inter-device agreement was investigated with Bland-Altman statistics. Conversion formulas were developed with linear regression. Diagnostic performances were evaluated with area under the receiver operating characteristic curves. RESULTS: Both SD-OCT and SS-OCT detected a significant pRNFL and mGCIPL thinning in glaucoma patients compared to HC and GS for almost all study sectors. A strong linear relationship between the two devices was present for all quadrants/sectors (R2 ≥ 0.81, P < 0.001), except for the nasal (R2 = 0.49, P < 0.001) and temporal (R2 = 0.62, P < 0.001) pRNFL quadrants. SD-OCT and SS-OCT measurements had a proportional bias, which could be removed with conversion formulas. Overall, the two devices showed similar diagnostic abilities. CONCLUSIONS: Thickness values obtained with SD-OCT and SS-OCT are not directly interchangeable but potentially interconvertible. Both devices have a similar ability to discriminate glaucoma patients from GS and healthy subjects. TRANSLATIONAL RELEVANCE: OCT-Angiography scans can be reliably used to obtain structural metrics in glaucoma patients

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC

Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature

ackground: Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults. Methods: A comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs. Results: Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p= 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p= 0.18). Conclusions: The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.The authors would like to acknowledge funding provided for the ongoing ATLANTIC randomized controlled trial supported by the National Health and Medical Research Council (NHMRC), Australia