Non-immediate drug hypersensitivity reactions secondary to intravitreal anti-vascular endothelial growth factors.

PURPOSE: To describe a series of non-immediate drug hypersensitivity reactions after intravitreal anti-vascular endothelial growth factors (anti-VEGFs). PATIENTS AND METHODS: Retrospective report of 6 patients with cutaneous non-immediate drug hypersensitivity reactions following intravitreal anti-VEGF injections, 4 after ranibizumab, 1 after bevacizumab and 1 after aflibercept. RESULTS: Clinical manifestations ranged from mild maculopapular rash, purpura to severe generalized erythroderma, with or without systemic involvement such as microscopic hematuria and proteinuria or fever. In two out of the six patients, reintroduction of either the same or an alternative anti-VEGF drug did induce a recurrence of the drug hypersensitivity reaction, while 4 patients showed no recurrence. CONCLUSION: Cutaneous non-immediate drug hypersensitivity reactions secondary to intravitreal anti-VEGF may occur. Continuation of the same drug or switch to another anti-VEGF may either induce recurrence or be well supported by the patient. The decision of drug discontinuation should be guided by the severity of the disease.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

A qualitative study of adolescents with medically unexplained symptoms and their parents. Part 2: How is healthcare perceived?

Medically unexplained symptoms (MUS) are common among adolescents and an important cause of clinical visits. This study sought to understand the experiences with, and perceptions of, the healthcare of adolescents who have MUS and their parents. Using a qualitative approach, six focus groups and two individual interviews were conducted with a total of ten adolescents and sixteen parents. The participants were recruited in a university hospital in Switzerland. A thematic analysis was conducted in accordance with the Grounded Theory. Six main themes emerged: needing a label for the symptoms, seeking an etiology to explain the symptoms, negotiating the medical system, medication and treatments, interactions with doctors, and the inclusion of parents during consultations. Transcending these themes, however, was the need for good communication between the adolescents, their parents and the clinicians. When explaining the symptoms, clinicians should make sure to discuss the results, investigations and lack of organic origin.

Recurrent Macular Edema in Central Retinal Vein Occlusion Treated with Intravitreal Ranibizumab using a Modified Treat and Extend Regimen.

BACKGROUND: The aim of this study was to evaluate the stability over time of the individually defined interval of intravitreal ranibizumab injection (IVR) for the treatment of recurrent macular edema (ME) in central retinal vein occlusion (CRVO). PATIENTS AND METHODS: A case series of treatment naïve patients followed in the Jules Gonin Eye Hospital for macular edema due to central retinal vein occlusion is presented. Patients were treated monthly with IVR until complete absence of fluid on qualitative SD-OCT with a minimum of 5 monthly IVR. Thereafter, they were followed according to a modified treat and extend regimen (mTER). RESULTS: Twelve eyes (12 patients) with ME due to CRVO were included. The mean follow-up period was 31.3 months. Analysis showed that best corrected visual acuity (BCVA), central macular thickness and qualitative spectral domain optical coherence tomography (SD-OCT) showed comparable results under monthly interval, after titration of an individualized interval and when performed in a series. 78% of treating intervals were within ±2 weeks of the first individually adjusted interval. The mean first defined interval was 4.3 weeks and the mean interval over time was 5.5 weeks (p=0.003). There was a trend towards longer interval over time. CONCLUSION: The adjusted interval of retreatment of patients with ME due to CRVO showed a high stability with a trend toward longer duration over time. An mTER regimen seems to be valuable to follow patients with ME with good stabilization of VA.

Long-term follow-up of choroidal neovascularization in pathological myopia treated with intravitreal ranibizumab.

BACKGROUND: The purpose of this contribution is to report our functional results on the efficacy of intravitreal ranibizumab for submacular choroidal neovessels (CNV) in high myopia, and to compare the roles of optical coherence tomography (OCT), fluorescein angiography and visual acuity changes in the treatment decision prior to each injection. PATIENTS AND METHODS: This is a retrospective study performed in Jules Gonin Eye Hospital. It included all patients with myopic CNV treated with intravitreal ranibizumab injections with a minimum follow-up of 24 months. After an induction dosing from 1 to 3 injections, the follow-up was based on a pro re nata regimen. Ophthalmic evaluation, best corrected visual acuity, and OCT were done at each visit, and fluorescein angiography at baseline and if neovascular activity was suspected. Retreatment criteria included metamorphopsia, visual loss of ≥5 ETDRS letters, any fluid on OCT and/or leakage on fluorescein angiography. RESULTS: 24 eyes were included in the study. Mean follow-up was 49 months. Mean visual acuity improved significantly from 62.8±13.8 letters at baseline to 72.8±12.9 letters at last follow-up visit (p=0.001). The mean number of injections was 2.2 in the first year and below 1 for the following years. The sensitivities of fluorescein angiography, SD OCT, and visual acuity loss≥5 letters were 62.6%, 51.4%, and 40%, respectively. The fluorescein angiography showed a significantly higher sensitivity in treatment decision than OCT (p=0.007). CONCLUSION: Our study has shown that ranibizumab injections provide a significant long-term visual benefit in myopic CNV with a small number of injections. Fluorescein angiography has a preponderant role in the treatment decision of active myopic CNV.

Painless indirect argon laser in high risk proliferative diabetic retinopathy.

BACKGROUND: Proliferative retinopathy is an important cause of vision loss in diabetic patients. Incomplete panretinal photocoagulation (PRP) can lead to recurrent proliferation of new vessels. PATIENTS AND METHODS: We retrospectively analysed the outcome of patients with high risk proliferative diabetic retinopathy (PDR) previously treated with slit lamp PRP who underwent indirect fill in argon laser treatment with scleral indentation under anesthesia for persistent neovascular proliferation. RESULTS: Seventeen eyes of ten patients were included. The mean age at diabetes onset was 17.3 years SD 16.2 (range 2-44). All patients reported long standing poor glycemic control (mean HbA1c: 8.5% SD 1.3 range 5.9-10.2). The area of retinal ischemia decreased significantly from 15±7.5 disk areas (DA) before fill-in laser to 3.2±4.2 DA after fill-in laser (p=0.001). The new vessels also regressed significantly after laser treatment 8.6±6.1 DA before treatment versus 6.5±6.4 DA after laser treatment, (p=0.044). Quiescent PDR was reached in 10 eyes (58.8%) at the last visit. CONCLUSIONS: Fill-in indirect argon laser under general anesthesia should be considered to achieve further new vessels regression in high risk PDR patients. Scleral indentation and absence of pain may allow for more extensive laser application.

The effect of switching ranibizumab to aflibercept in refractory cases of macular edema secondary to ischemic central vein occlusion.

BACKGROUND: Macular edema resulting from central retinal vein occlusion is effectively treated with anti-vascular endothelial growth factor injections. However, some patients need monthly retreatment and still show frequent recurrences. The purpose of this study was to evaluate the visual and anatomic outcomes of refractory macular edema resulting from ischemic central retinal vein occlusion in patients switched from ranibizumab to aflibercept intravitreal injections. PATIENTS AND METHODS: We describe a retrospective series of patients followed in the Medical Retina Unit of the Jules Gonin Eye Hospital for macular edema due to ischemic central retinal vein occlusion, refractory to monthly retreatment with ranibizumab, and changed to aflibercept. Refractory macular edema was defined as persistence of any fluid at each visit one month after last injection during at least 6 months. All patients had to have undergone pan-retinal laser scan. RESULTS: Six patients were identified, one of whom had a very short-term follow-up (excluded from statistics). Mean age was 57±12 years. The mean changes in visual acuity and central macular thickness from baseline to switch were +20.6±20.3 ETDRS letters and -316.4±276.6 µm, respectively. The additional changes from before to after the switch were +9.2±9.5 ETDRS letters and -248.0±248.7 µm, respectively. The injection intervals could often be lengthened after the switch. CONCLUSIONS: Intravitreal aflibercept seems to be a promising alternative treatment for macular edema refractory to ranibizumab in ischemic central retinal vein occlusion.

[Transition to adult care: an overview]. / Transition aux soins adultes: une vue d'ensemble.

Nowadays nearly 90% of children with a chronic condition survive to adulthood and must make the transition from pediatric to adult care. This transition must include not only the continuity of care but also the preparation for adult life so that these young people can develop their full potential. Divided into three phases (preparation, transfer and engagement), the transition process should be adapted to adolescents and ensure access to quality care.

The health of adolescents around a world in transition.

Since several years, the health of adolescents is on the agenda of ministers, decision makers and health professionals. Around the world, while there has been a steady decrease of the death rates among young children, this is not the case for young people. This is mainly linked with the fact that mortality and morbidity during this period of life is largely linked with non communicable diseases and conditions, including deaths from injuries, suicide, homicides and drug abuse. Unplanned pregnancies, illegal abortions, newly acquired HIV infections are also situations that have short and long term consequences. This paper reviews the epidemiological data pertaining to adolescent health and disease. It proposes evidence-informed avenues as how to address these issues in the field of health care (e.g. adolescent friendly services) and of prevention and health promotion. It also stresses the importance of creating safe environments for the development and well-being of young people and thus, of an interdisciplinary and inter sectorial approach to their complex health problems and challenges.

Intravitreal dexamethasone implant for the treatment of macular edema after retinal vein occlusion in a clinical setting.

BACKGROUND: To study the efficacy and safety of a new intravitreal implant (sustained release of dexamethasone, Ozurdex®) recently approved in Switzerland for the treatment of macular edema secondary to retinal vein occlusion in a clinical setting. PATIENTS AND METHODS: Prospective non-consecutive study of patients with macular edema secondary to central retinal vein occlusion or branch retinal vein occlusion treated with implant of dexamethasone 0.7 mg. Follow-up visits were performed at day 1, week 1 and monthly thereafter. ETDRS best corrected visual acuity, Goldmann tonometry and macular thickness on SD-OCT were registered. Retreatment was carried out on a pro re nata basis starting from month 3. RESULTS: Fifteen eyes of 15 patients were included (8 branch retinal vein occlusions, 7 central retinal vein occlusions). 33% of the patients achieved 3 lines or more of vision gain. The central retinal vein occlusion subgroup showed a mean decline in visual acuity at month 3. A reduction of 36% of macular edema was already observed at day 1. All maculae were dry at month 1. The mean time of recurrence of macular edema for both groups was 4.6 months. A similar reduction of macular edema was obtained after a second implantation. An intraocular pressure increase of ≥ 20% was observed after the first implantation in 53% of patients. CONCLUSION: Our study showed efficacy and safety of intravitreal dexamethasone implant in the treatment of macular edema due to retinal vein occlusion. Anatomical efficacy was observed at day 1 but seems to have shorter effect than previously published data. No serious side effects were observed.

Comparison of fundus autofluorescence images acquired by the confocal scanning laser ophthalmoscope (488 nm excitation) and the modified Topcon fundus camera (580 nm excitation).

To compare autofluorescence (AF) images obtained with the confocal scanning laser ophthalmoscope (using the Heidelberg retina angiograph; HRA) and the modified Topcon fundus camera, in a routine clinical setting. A prospective comparative study conducted at the Jules-Gonin Eye Hospital. Fifty-six patients from the medical retina clinic. All patients had complete ophthalmic slit-lamp and fundus examinations, colour and red-free fundus photography, AF imaging with both instruments, and fluorescein angiography. Cataract and fixation were graded clinically. AF patterns were analyzed for healthy and pathological features. Differences of image noise were analyzed by cataract grading and fixation. A total of 105 eyes were included. AF patterns discovered by the retina angiograph and the fundus camera images, respectively, were a dark optic disc in 72 % versus 15 %, a dark fovea in 92 % versus 4 %, sub- and intraretinal fluid visible as hyperautofluorescence on HRA images only, lipid exudates visible as hypoautofluorescence on HRA images only. The same autofluorescent pattern was found on both images for geographic atrophy, retinal pigment changes, drusen and haemorrhage. Image noise was significantly associated with the degree of cataract and/or poor fixation, favouring the fundus camera. Images acquired by the fundus camera before and after fluorescein angiography were identical. Fundus AF images differ according to the technical differences of the instruments used. Knowledge of these differences is important not only for correctly interpreting images, but also for selecting the most appropriate instrument for the clinical situation.

The importance of monitoring wet age-related macular degeneration patients during Coronavirus disease 19 pandemic: A retrospective study of assessment of functional and structural outcomes.

OBJECTIVES: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2). METHODS: Wet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of≥5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit. MAIN RESULTS: Group 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P=0.04, P<0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P=0.03 and P=0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome. CONCLUSIONS: The cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained.

Intravitreal ranibizumab in the treatment of predominantly hemorrhagic lesions in exudative age-related macular degeneration.

BACKGROUND: Submacular hemorrhage is a manifestation of neovascular age-related macular degeneration (AMD) that has a very poor natural history leading to severe visual loss. We have evaluated the safety and efficacy of intravitreal ranibizumab in the treatment of predominantly hemorrhagic AMD. PATIENTS AND METHODS: A retrospective study of patients with predominantly hemorrhagic AMD treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between December 2006 and December 2008 was undertaken. Baseline and monthly follow-up exams included visual acuity (VA), fundus exam and optical coherence tomography (OCT) while fluorescein and indocyanine green angiography were performed at least every three months. RESULTS: The study included 8 eyes. The mean follow-up was 13 months (SD: 6.3). The mean number of intravitreal injections administered for each patient was 6.4 (SD: 2). 50 % of the patients demonstrated stable or improved VA. The size of hemorrhage at baseline was inversely correlated to the final VA (two-tailed p value = 0.038) and positively correlated to the final central macular thickness (two-tailed p value = 0.021). Anticoagulation treatment was inversely correlated to the time of hemorrhage resolution (two-tailed p value = 0.039). CONCLUSIONS: Intravitreal ranibizumab may be an effective treatment for predominantly hemorrhagic lesions due to neovascular AMD.

Perifoveal capillary changes in diabetic patients and association between severity and type of diabetes, visual acuity, and enlargement of non-flow area in the retinal capillary plexuses.

BACKGROUND: The goal of this study was to evaluate the perifoveal capillary bed and to analyze areas of non-flow using optical coherence tomography angiography (OCT-A) in patients presenting with diabetic retinopathy (DR), correlating them to the severity of DR, type of diabetes and visual acuity (VA). PATIENTS AND METHODS: The non-flow area (NFA) and foveal avascular zone (FAZ) in the superficial (SCP) and deep capillary plexus (DCP) were calculated using OCT-A imaging of patients with DR followed between July 2015 and March 2016 at the Jules Gonin Eye Hospital (Lausanne, Switzerland). Disease severity was classified using the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Analysis of variance was used to correct for correlation between eyes. RESULTS: Seventy-eight eyes of 53 patients were included (29 men; 44 right eyes). There were 45 eyes with non-proliferative DR (NPDR; stage 1 [n=14], stage 2 [n=7], and stage 3 [n=24]) and 33 with proliferative DR (PDR; stage 1 [n=17], stage 2 [n=16]) included, among which 26 had type I diabetes and 52 type II diabetes. The mean Best Corrected Visual Acuity (BCVA) was 78.5 letters. The mean NFA in the SCP differed according to diabetes type and stage of DR (type 1 diabetes: NPDR, 0.76±0.3, PDR, 1.24±0.7; type 2 diabetes: NPDR, 1.46±0.7, PDR, 1.57±0.7). CONCLUSION: The NFA, measured by OCTA, may be a useful indicator of DR severity, especially in the superficial capillary plexus. Loss of visual acuity might be correlated with increasing NFA (excluding the FAZ or not), primarily among patients with type II diabetes and NPDR.

[Caring for unaccompanied minors: an experience from Lausanne]. / Soins aux mineurs non accompagnés (MNA): l'expérience lausannoise.

Medical treatment of an unaccompanied minor is made more complicated firstly by its connections with the politics of immigration and secondly by the difficulty in gaining recognition of the priority of the minor's interests. Enabling healthcare teams to travel and meet these particularly vulnerable youths makes medical care more accessible to them and facilitates an optimal bio-psycho-social treatment. For most of these adolescents it is their lack of plans for the future which remains the major obstacle to their development and mental and physical health.

www.fevertravel.ch: an online study prototype to evaluate the safety and feasibility of computerized guidelines for fever in returning travellers and migrants.

Following the paper publication of practice guidelines for the management of febrile patients returning from the tropics, we constructed a consultation website that comprises a decision chart and specific diagnostic features providing medical diagnostic assistance to primary care physicians. We then integrated a research component to evaluate the implementation of these computerized guidelines. This study website has the same interface as the consultation website. In addition, one is able to record: (i) the pathway followed by the physician through the decision chart, (ii) the diagnostic tests performed, (iii) the initial and final diagnoses as well as outcome and (iv) reasons for non-adherence when the physician diverges from the proposed attitude. We believe that Internet technology is a powerful medium to reach physicians of different horizons in their own environment, and could prove to be an effective research tool to disseminate practice guidelines and evaluate their appropriateness. Here we describe the design, content, architecture and system implementation of this interactive study prototype aimed at integrating operational research in primary care practice.

Retinal angiomatous proliferation treated with a combination of intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin.

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.