Nepafenac for cystoid macular oedema secondary to paclitaxel.

Paclitaxel is used to treat a wide range of malignant tumours. This type of drug is known to cause ocular adverse effects, with cystoid macular oedema being a known, but rare complication, of this therapy. Although most cases resolve after discontinuation of the drug, several authors have attempted various treatments to accelerate resolution, or when paclitaxel therapy cannot be discontinued. A case is presented of a 62 year-old man who presented with decreased visual acuity due to bilateral cystoid macular oedema after administration of paclitaxel for oesophageal cancer. As part of the study, optical coherence tomography angiography (OCTA) was performed at the time of diagnosis, and later when the symptoms subsided. Nepafenac eye drops were prescribed as treatment.

Time to relapse after tildrakizumab withdrawal in patients with moderate-to-severe psoriasis who were responders at week 28: post hoc analysis through 64 weeks from reSURFACE 1 trial.

BACKGROUND: As treatment interruptions occur during psoriasis management in clinical practice, it is important to know the duration of clinical response after treatment withdrawal. OBJECTIVES: To report time to and predictors of relapse in patients who were tildrakizumab 100 and 200 mg responders (≥75% improvement in Psoriasis Area and Severity Index, PASI 75) at week 28 re-randomized to placebo from reSURFACE 1 trial. METHODS: Post hoc analysis of adult patients with moderate-to-severe plaque psoriasis from a 64-week phase 3 trial. Relapse was primarily defined as loss of PASI 75 response. Both relapses defined as loss of PASI 90 and loss of absolute PASI < 2 response were included as sensitivity analyses. PASI 75, PASI 90 and PASI < 2 responders re-randomized to placebo at week 28 and followed up until week 64 were included. The Kaplan-Meier (KM) estimates of the 64-week relapse rate were calculated. The log-rank test to compare KM curves from responders to tildrakizumab 100 and 200 mg was used. Independent predictors of relapse were explored. RESULTS: Median time to loss of PASI 75/PASI 90/PASI < 2 response from week 28 was 142/111/112 days with tildrakizumab 100 mg and 172/140/113 days with tildrakizumab 200 mg, respectively (all not significant). Around 20% of patients did not relapse (either maintained a PASI 75 response or were lost to follow-up) during the 36-week period. Increase in body mass index (BMI) (hazard ratio, HR [95% confidence interval, CI] for loss of PASI 75 response: 1.0345 [1.0112-1.0582]) and increase in disease duration (HR [95% CI]: 1.0151 [1.0028-1.0275] for loss of PASI 75 response) were associated with an increased risk of relapse, regardless of the relapse definition. CONCLUSIONS: When treatment is interrupted, tildrakizumab provides durable maintenance of efficacy with a median time to loss of PASI 75 response of 5-6 months, irrespective of the dose. Interventions on modifiable risk factors for relapse, such as BMI, may improve personalized long-term psoriasis management.

MEK Retinopathy. Clinical case reports. / Retinopatía MEK. Casos clínicos.

CASE REPORTS: Three clinical cases are presented of MEK retinopathy associated with the combination of cobimetinib and vemurafenib characterised by alteration of the retinal pigment epithelium and neurosensory detachment. Two of the cases conserved the vision of the unit, and the third developed a large bilateral neurosensory detachment with final visual acuity of 0.6 for the right eye and 0.1 for the left one. DISCUSSION: The new therapeutic strategies against metastatic cutaneous melanoma condition the appearance of alterations of the pigmentary epithelium of the retina with serous detachments, leading to close monitoring with macular optical coherence tomography.

MN1-Fli1 oncofusion transforms murine hematopoietic progenitor cells into acute megakaryoblastic leukemia cells.

Long-term outcome of acute megakaryoblastic leukemia (AMKL) patients without Down's syndrome remains poor. Founding mutations and chimeric oncogenes characterize various AMKL subtypes. However, for around one third of all cases the underlying mechanisms of AMKL leukemogenesis are still largely unknown. Recently, an in-frame fusion of meningeoma 1-friend leukemia virus integration 1 (MN1-Fli1) gene was detected in a child with AMKL. We intended to investigate the potential role of this oncofusion in leukemogenesis of acute myeloid leukemia. Strikingly, expression of MN1-Fli1 in murine hematopoietic progenitor cells was sufficient to induce leukemic transformation generating immature myeloid cells with cytomorphology and expression of surface markers typical for AMKL. Systematic structure function analyses revealed FLS and 3'ETS domains of Fli1 as decisive domains for the AMKL phenotype. Our data highlight an important role of MN1-Fli1 in AMKL leukemogenesis and provide a basis for research assessing the value of this oncofusion as a future diagnostic marker and/or therapeutic target in AMKL patients.

[A cost-effectiveness study of dexamethasone implants in macular edema]. / Resultados coste-efectividad del implante de dexametasona en edema macular.

OBJECTIVE: To analyze the cost-effectiveness and benefits of a dexamethasone intravitreal implant (Ozurdex®, Allergan, Irvine, CA, USA.) in its clinically relevant applications. MATERIAL AND METHODS: A total of 88 eyes of 86 patients with macular edema of > 300 µm measured by optical coherence tomography (Cirrus Zeiss, Dublin, CA, USA) were included in this two-year retrospective study, with a minimum of 6 months follow-up. The patients were divide into 3 groups: group 1 with macular edema in retinal vein occlusion, group 2 with non-infectious posterior uveitis, and group 3 with diabetic macular edema. The treatment was off-label but supported by the literature. Before implantation, and on days 1, 30, 60, 90 and 180, corrected visual acuity (Snellen), central retinal thickness, intraocular pressure and biomicroscopy were evaluated. The cost-benefit analysis was tabulated by line of visual acuity gained, comparing the main therapeutic alternatives and assessment of the safety profile of the dexamethasone intravitreal implant (Ozurdex®, Allergan, Irvine, CA, USA). RESULTS: The results of this study did not differ from the published studies, in terms of visual acuity improvement in 63.3% of cases, and with central macular thickness improvement in 97% of cases. There were relapses, which occurred after 120 days on average, and the need for retreatment was 40.9%. Increased intraocular pressure >23 mm Hg was among the side effects in 29.54%, and was controlled with topical treatment, except in 1.13% requiring surgical treatment. The development of cataract was 44.7%, and 10.6% required surgery. Treatment results showed less frequent use of Ozurdex® than other treatments for disease control, being a cost saving option. DISCUSSION: Cost-effectiveness analyses are clinically relevant when applying treatment strategies in patients with macular edema. Dexamethasone intravitreal implant appears to be a safe and efficient therapy.

[Guidelines of clinical practice of the SERV (Spanish Retina and Vitreous Society): management of ocular complications of diabetes. Diabetic retinopathy and macular oedema]. / Guías de práctica clínica de la SERV: manejo de las complicaciones oculares de la diabetes. Retinopatía diabética y edema macular.

OBJECTIVE: Diabetes mellitus is considered the most common cause of blindness in the working population of industrialized countries, with diabetic macular edema being the most common cause of decreased visual acuity and proliferative diabetic retinopathy (PDR) being responsible for the most severe visual deficits. We have therefore tried to establish a guide for clinical intervention whose purpose is to provide orientation on the treatment of diabetic retinopathy and its complications. This is necessary at a time when many treatment options have emerged whose role is not yet fully defined. METHOD: A group of expert retina specialists selected by the SERV (Vitreous-Retina Spanish Society) assessed the published results of different treatment options currently available, suggesting lines of action according to the degree of diabetic retinopathy present and the presence or absence of macular edema. RESULTS: PDR is primarily treated with pan-retinal photocoagulation. For clinically significant diabetic macular edema without signs of vitreomacular traction, the treatment of choice continues to be focal/grid photocoagulation. Similarly, retinovitreal surgery is indicated for both conditions. The use of antiangiogenic drugs was also analyzed but remains inconclusive. CONCLUSION: Laser therapy is effective in the management of diabetic retinopathy and diabetic macular edema. The role of antiangiogenics is not yet sufficiently defined.

[Review of the protocol for the treatment of diabetic retinopathy]. / Revisión del protocolo para el tratamiento de la retinopatía diabética.

We present general guidelines to help us with the treatment of diabetic retinopathy (DR) at a time when numerous therapeutic alternatives have been developed although their role has not yet been adequately defined. This protocol is not directed at experienced retinologists but rather at general ophthalmologists who require a practical and up to date guide of a pathology as prevalent as RD. The different therapeutic options available, and their most accepted indications depending on the degree of diabetic retinopathy that patients have, are reviewed. We propose what to do in cases of mild, moderate and severe non-proliferative diabetic retinopathy as well as in cases of proliferative diabetic retinopathy (panphotocoagulation/antiangiogenic drugs/vitreorretinal surgery). The treatment of diabetic macular edema depending on its angiographic and topographic characteristics is also discussed. The importance of metabolic control of the patient is stressed (tight glycemic control, control of arterial hypertension and dyslipemia) in aiding the treatment of diabetic retinopathy. This therapeutic proposal has been discussed widely by retinologists from the four largest hospitals in the Canary Islands, and is therefore an agreed text based on recent scientific literature.

Risk of selecting de novo drug-resistance mutations during structured treatment interruptions in patients with chronic HIV infection.

BACKGROUND: Structured treatment interruption (STI) may allow viral replication in the presence of decreased plasma drug levels, with risk of selection of resistance mutations. METHODS: For patients recruited for an STI study, genotypic resistance testing was performed at baseline (before receipt of any treatment), immediately before the STI, and 2 weeks after each interuption of therapy. RESULTS: During 20 (18%) of 112 STI cycles (95% CI, 11%-26%), resistance mutations were selected; 6% of the mutations were de novo (i.e., not detected before the start of STI), and 12% were archived mutations (i.e., mutations already detected before the STI). Overall, resistance mutations during STI were selected in 9 (26%) of 35 patients; 5 (14%) of the mutations were de novo, and 4 (12%) were archived mutations. Mutations conferring resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) were selected in 3 (23%) of 13 patients receiving NNRTI-based regimens (all mutations were de novo). Mutations conferring resistance to lamivudine were selected in 9 (50%) of 18 patients receiving lamivudine-containing regimens (4 [22%] were de novo, and 5 [28%] were archived mutations). Mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs), excluding the M184V mutation, were selected in 2 (6%) of 35 recipients of NRTIs (1 [3%] of these mutations was de novo, and 1 [3%] was an archived mutation. Finally, mutations conferring resistance to protease inhibitors were selected in none of the 22 patients receiving protease inhibitors. In most cases, de novo and archived mutations were selected during the first STI cycle, and their number did not increase during successive cycles. Plasma viral load decreased to undetectable levels in all the patients when the earlier drug regimen was reintroduced. CONCLUSIONS: Genotypic mutations are selected during STI in a high proportion of patients (especially in patients receiving NNRTIs or lamivudine). Approximately one-half of selected mutations were archived mutations. Patients who had archived mutations did not have a higher risk of accumulating new mutations than did patients who were infected with wild-type virus before the STI.

New patterns of HIV-1 resistance during HAART.

HIV-1 resistance and subsequent virologic failure occur in a substantial proportion of HIV-infected patients receiving HAART regimens. In the present article, we summarize new data on resistance to current and forthcoming antiretroviral drugs which will help in the interpretation of the results of resistance tests and the individualization of therapy. Nucleoside analog mutations (NAMs) (M41L, D67N, K70R, L210W, T215Y/F and K219Q/E) are associated with reduced susceptibility to most nucleoside analogs and the nucleotide tenofovir. This recently approved drug has shown a reduced virologic response in the presence of three or more NAMs, including M41L or L210W, as well as in the presence of T69 insertions. Hypersusceptibility (IC50 < 0.5) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) has recently been described in association with increased resistance to nucleoside analogs, and it seems to enhance the immunologic and virologic reponses in patients receiving efavirenz-containing regimens. New protease inhibitors (PIs) have a lower cross-resistance profile, although more clinical data are needed to establish appropriate PI sequencing to promote sustained virologic success. Cross-resistance between amprenavir (APV) and lopinavir (LPV/r) in the presence of only four APV-related mutations has been described, suggesting that phenotypic tests should be applied before prescribing LPV/r to APV-experienced patients. Resistance to the new entry inhibitor class compound T-20 (enfuvirtide) has also been detected.

The role of nevirapine in the treatment of HIV-1 disease.

Nevirapine (Viramune, Boehringer Ingelheim) is a non-nucleoside reverse transcriptase (RT) inhibitor (NNRTI) effective in the treatment of HIV-1 infected antiretroviral-naive and -experienced patients. Some recent studies have suggested that nevirapine-based regimens may have an efficacy similar to protease inhibitor (PI)-based regimens, at least in naive patients with CD4+ > 200 microl, while it lacks the drawbacks inherent in PI-containing regimens, such as lipodystrophy and metabolic alterations. Switching from a PI-containing regimen to a nevirapine-containing regimen seems to retain the virological response to therapy and it may also limit or reverse the development of some metabolic disorders induced by PIs. Nevirapine is also effective in preventing mother-to-child transmission of HIV-1 disease and in the treatment of HIV-1 infected children. Nevirapine is well-tolerated, rash being the most common severe adverse effect observed. Hepatotoxicity may also appear with nevirapine, mainly in patients with chronic hepatitis C and/or altered liver function tests. This side effect may occasionally be life-threatening but it can be safely managed in most patients.