The Effects of Treatment Regimen on the Initial Management of Macular Neovascularization Subtypes in Age-Related Macular Degeneration.

INTRODUCTION: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype. METHODS: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes. RESULTS: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045). CONCLUSION: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden.

Characterization of the Skeletal Muscle Proteome in Undernourished Old Rats.

Aging is associated with a progressive loss of skeletal muscle mass and function termed sarcopenia. Various metabolic alterations that occur with aging also increase the risk of undernutrition, which can worsen age-related sarcopenia. However, the impact of undernutrition on aged skeletal muscle remains largely under-researched. To build a deeper understanding of the cellular and molecular mechanisms underlying age-related sarcopenia, we characterized the undernutrition-induced changes in the skeletal muscle proteome in old rats. For this study, 20-month-old male rats were fed 50% or 100% of their spontaneous intake for 12 weeks, and proteomic analysis was performed on both slow- and fast-twitch muscles. Proteomic profiling of undernourished aged skeletal muscle revealed that undernutrition has profound effects on muscle proteome independently of its effect on muscle mass. Undernutrition-induced changes in muscle proteome appear to be muscle-type-specific: slow-twitch muscle showed a broad pattern of differential expression in proteins important for energy metabolism, whereas fast-twitch muscle mainly showed changes in protein turnover between undernourished and control rats. This first proteomic analysis of undernourished aged skeletal muscle provides new molecular-level insight to explain phenotypic changes in undernourished aged muscle. We anticipate this work as a starting point to define new biomarkers associated with undernutrition-induced muscle loss in the elderly.

Femtosecond laser-assisted versus phacoemulsification cataract surgery (FEMCAT): a multicentre participant-masked randomised superiority and cost-effectiveness trial.

BACKGROUND: Cataract surgery is one of the most common operations in health care. Femtosecond laser-assisted cataract surgery (FLACS) enables more precise ocular incisions and lens fragmentation than does phacoemulsification cataract surgery (PCS). We hypothesised that FLACS might improve outcomes in cataract surgery compared with PCS despite having higher costs. METHODS: We did a participant-masked randomised superiority clinical trial comparing FLACS and PCS in two parallel groups (permuted block randomisation stratified on centres via a centralised web-based application, allocation ratio 1:1, block size of 2 or 4 for unilateral cases and 2 or 6 for bilateral cases). Five French University Hospitals enrolled consecutive patients aged 22 years or older who were eligible for unilateral or bilateral cataract surgery. Participants, outcome assessors, and technicians carrying out examinations were masked to the surgical treatment allocation until the last follow-up visit and a sham laser procedure was set up for participants randomly assigned to the PCS arm. The primary clinical endpoint was the success rate of surgery, defined as a composite of four outcomes at a 3-month postoperative visit: absence of severe perioperative complication, a best-corrected visual acuity (BCVA) of 0·0 LogMAR (logarithm of the minimum angle of resolution) or better, an absolute refractive error of 0·75 dioptres or less, and unchanged postoperative corneal astigmatism power (≤0·5 dioptres) and axis (≤20°). The primary economic endpoint was the incremental cost per additional patient who had treatment success at 3 months. Primary outcomes were assessed in all randomly assigned patients who met all eligibility criteria (missing data considered as failure). We used mixed logistic regression models or mixed linear regression models for statistical comparisons, adjusted on centres and whether cataract surgery was bilateral or unilateral. The study is registered with ClinicalTrials.gov, NCT01982006. FINDINGS: Of the 907 patients (1476 eyes) randomly assigned between Oct 9, 2013, and Oct 30, 2015, 870 (704 eyes in FLACS group and 685 eyes in the PCS group) were analysed. We identified no significant difference in the success rate of surgery between the FLACS and PCS groups (FLACS: 41·1% [289 eyes]; PCS: 43·6% [299 eyes]); adjusted odds ratio 0·85, 95% CI 0·64-1·12, p=0·250). The incremental cost-effectiveness ratio was €10 703 saved per additional patient who had treatment success with PCS compared with FLACS. We observed no severe adverse events during the femtosecond laser procedure, and most of the complications in the FLACS group related to the primary outcome measures occurred during the phacoemulsification phase or postoperatively. INTERPRETATION: Despite its advanced technology, femtosecond laser was not superior to phacoemulsification in cataract surgery and, with higher costs, did not provide an additional benefit over phacoemulsification for patients or health-care systems. FUNDING: French Ministry of Social Affairs and Health.

QUANTITATIVE ANALYSIS OF CHORIOCAPILLARIS ALTERATIONS IN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN DIABETIC PATIENTS.

PURPOSE: To evaluate quantitative alterations of the choriocapillaris in swept-source optical coherence tomography angiography in diabetic patients. METHODS: We included normal patients and diabetic patients with and without diabetic retinopathy (DR), excluding patients with macular edema. Angiograms in 3 × 3 mm were acquired with Plexelite 9000 swept-source optical coherence tomography angiography. Choroidal flow voids were analyzed after removal of projection artifacts. The main evaluation was the correlation between choroidal flow voids area (FVA-CC) and DR stage. RESULTS: A total of 120 eyes of 72 patients were analyzed. There were 17 eyes from healthy subjects, 30 eyes without DR, 22 eyes with minimal nonproliferative DR, 30 eyes with moderate nonproliferative DR, 16 eyes with severe nonproliferative DR, and 5 eyes with proliferative DR (PDR). The percentage of FVA-CC for each group was, respectively, 10.9 ± 3.4%, 14.6 ± 4.8%, 17.6 ± 3.5%, 20.7 ± 5.9%, 19.9 ± 2.9%, and 26.6 ± 4.4%. FVA-CC and DR stage significantly correlated (P < 0.0001). FVA-CC was significantly increased in diabetic patients without DR compared with healthy subjects (P = 0.008). CONCLUSION: Diabetes is associated with quantifiable choriocapillaris alterations in swept-source optical coherence tomography angiography. These alterations precede clinical signs of DR and are correlated with DR stage.

LONG-TERM INCIDENCE AND RISK FACTORS OF OCULAR HYPERTENSION FOLLOWING DEXAMETHASONE-IMPLANT INJECTIONS: THE SAFODEX-2 STUDY.

PURPOSE: To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation. METHODS: Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure. RESULTS: Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3-62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P = 0.248). CONCLUSION: This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.

UVEITIS TREATED WITH DEXAMETHASONE IMPLANT.

PURPOSE: To evaluate the real-life efficacy and safety of the intravitreal dexamethasone implant in uveitis. METHODS: This retrospective observational multicentric study included 152 eyes treated exclusively by 358 dexamethasone implant injections. The main outcome measures included change in the best-corrected visual acuity, central macular thickness, and vitreous haze score. RESULTS: Patients were treated with dexamethasone implant for macular edema (51.3%), vitritis with macular edema (40.1%), vitritis (5.3%), and other causes (3.3%). The mean duration of follow-up was 19.0 months. The mean gain in best-corrected visual acuity during follow-up was +12.1 letters. An improvement in best-corrected visual acuity ≥5, 10, and 15 letters was found in 64.5, 50.7, and 35.5% of cases, respectively. 59.7% of eyes with macular edema at baseline were found to be anatomical responders. Vitritis resolution (vitreous haze = 0+) was obtained in 81.4% of cases. Ocular hypertension (intraocular pressure ≥25 mmHg and/or gain ≥10 mmHg from baseline) occurred in 28.3% of patients. No filtering surgery/laser therapy was required. A total of 40.2% of phakic subjects underwent cataract surgery on average 11.2 months after the first injection. CONCLUSION: This study confirms the efficacy and safety of the dexamethasone implant in noninfectious uveitis. Cataract and ocular hypertension were not uncommon but easily manageable.

HYPERAUTOFLUORESCENT SPOTS IN ACUTE OCULAR TOXOPLASMOSIS: A New Indicator of Outer Retinal Inflammation.

PURPOSE: The aim of this study was to describe the fundus autofluorescence patterns in acute ocular toxoplasmosis (OT) and to correlate these findings with other imaging. METHODS: A retrospective multicenter case series of 27 eyes from 27 patients with acute onset of posterior OT was conducted. Multimodal imaging including fundus autofluorescence was performed at diagnosis and during follow-up. RESULTS: All OT lesions were hypoautofluorescent on fundus autofluorescence imaging. Fourteen patients (51.8%) also had hyperautofluorescent spots around the active foci that disappeared after retinal photobleaching. Although these spots were not seen on early phase of indocyanine green angiography, they become hypofluorescent in the late phase without choriocapillaris flow impairment on optical coherence tomography angiography. On B-scan spectral domain optical coherence tomography, spots corresponded to outer retinal alterations in all cases. All hyperautofluorescent spots disappeared during follow-up as acute OT resolved. Younger patients and those with more posterior inflammatory symptoms (vasculitis and/or papillitis) were more frequent with the presence of hyperautofluorescent spots. CONCLUSION: Ocular toxoplasmosis may trigger a transient outer retinal disruption in eyes with marked inflammatory symptoms of the younger patients.

Nutritional evaluation of mixed wheat-faba bean pasta in growing rats: impact of protein source and drying temperature on protein digestibility and retention.

This study aimed to evaluate the nutritional value of pasta enriched with legume or wheat gluten proteins and dried at varying temperature. A total of four isonitrogenous experimental diets were produced using gluten powder/wheat semolina (6/94, g/g) pasta and faba bean flour/wheat semolina (35/65, g/g) pasta dried at either 55°C (GLT and FLT, respectively) or 90°C (FVHT and GVHT, respectively). Experimental diets were fed to ten 1-month-old Wistar rats (body weight=176 (sem 15) g) for 21 d. Growth and nutritional, metabolic and inflammatory markers were measured and compared with an isonitrogenous casein diet (CD). The enrichment with faba bean increased the lysine, threonine and branched amino acids by 97, 23 and 10 %, respectively. Protein utilisation also increased by 75 % (P<0·01) in FLT in comparison to GLT diet, without any effect on the corrected faecal digestibility (P>0·05). Faba bean pasta diets' corrected protein digestibility and utilisation was only 3·5 and 9 %, respectively, lower than the CD. Growth rate, blood composition and muscle weights were not generally different with faba bean pasta diets compared with CD. Corrected protein digestibility was 3 % lower in GVHT than GLT, which may be associated with greater carboxymethyllysine. This study in growing rats clearly indicates improvement in growth performance of rats fed legume-enriched pasta diet compared with rats fed gluten-wheat pasta diet, regardless of pasta drying temperature. This means faba bean flour can be used to improve the protein quality and quantity of pasta.

Comparison of 20-gauge Procore® and 22-gauge Acquire® needles for EUS-FNB of solid pancreatic masses: an observational study.

Background and Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has been proposed to obtain high-quality tissue samples for pancreatic tumors. We performed an observational study to compare EUS-FNB with a 20-gauge Procore® needle versus a 22-gauge Acquire® needle. Our primary endpoint was the quantity of the obtained tissue, as defined by the mean cumulative length of tissue core biopsies per needle pass. Methods: Sixty-eight EUS-FNB were consecutively performed on patients with a pancreatic mass. The choice of needle depended on availability at the time of admission: 34 punctures were performed with each needle. Histological material was studied in a blinded manner with respect to the needle, and the cumulative length of tissue core biopsies per needle pass was determined. Intraobserver and interobserver variability of this criterion was then evaluated. Results: There were no between-group differences. Histological diagnosis was achieved and core biopsy specimens were obtained in 28 out of 34 patients (82%) in the 20-gauge Procore® group and in 33 out of 34 patients (97%) in the 22-gauge Acquire® group (p = .1). The mean cumulative length of tissue core biopsies per needle pass was significantly higher with the 22-gauge Acquire® needle with 8.2 ± 4.2 mm versus 4.2 ± 3.8 mm for the 20-gauge Procore® needle (p < .01). No intra and inter-observer variability of this criterion was observed. Conclusions: Our results suggest significant differences, with a mean cumulative length of tissue core biopsies per needle pass significantly higher with the 22-gauge Acquire® needle. This simple criterion seems reliable and reproducible.

Increased choroidal thickness: a new feature to monitor age-related macular degeneration recurrence.

PURPOSE: The main objective of this study was to assess choroidal thickness (CT) changes during an exudative recurrence of age-related macular degeneration (AMD). METHODS: A real-life prospective non-interventional 9-month study was conducted in two centers in consecutive patients with exudative AMD between November 2016 and July 2017. CT was measured manually in both eyes based on enhanced-depth imaging spectral-domain optical coherence tomography at different follow-up visits scheduled in the morning. RESULTS: A total of 134 patients were included. Ninety-five patients presented at least one episode, defined by a follow-up visit under controlled condition (dry retina) followed by a visit for exudative recurrence. A total of 119 episodes were analyzed. The mean CT change in the treated eye was + 8.45 ± 13.52 µm (p < 0.001) and + 5.62 ± 14.77 µm (p = 0.009) respectively in the subfoveal area and nasal area. No significant change in CT was observed in the fellow eye. No significant association between CT changes and treatment, number of intravitreal injections, and blood pressure was observed. CONCLUSION: CT increased in case of exudative recurrence of neovascular AMD. The increase was mild but significant. Thus, CT could be used as a monitoring criterion, like the central retinal thickness, in AMD management.

EVALUATION OF OBSTRUCTIVE SLEEP APNEA SYNDROME AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE II DIABETES.

PURPOSE: To evaluate the association between obstructive sleep apnea and diabetic macular edema (DME) in patients with Type II diabetes, using the apnea-hypopnea index and other nocturnal hypoxemia parameters. METHODS: This cross-sectional, case-control study included 99 patients with Type II diabetes: the first group included patients with DME (DME+ group) and the second patients without DME (DME- group). Polysomnography was performed in all patients. The two groups were compared, and the risk factors were studied using logistic regression. RESULTS: The DME+ group comprised 38 patients, and the DME- group comprised 61 patients, aged a mean 68.8 years and 66.3 years (P = 0.27), respectively; mean body mass index was 29.7 and 30.9 (P = 0.16), respectively. The mean apnea-hypopnea index was significantly higher in the DME+ group (43.95 [13.5-87.3]) than in the DME- group (35.18 [3.55-90.7]) (P = 0.034). Patients with DME had more severe obstructive sleep apnea (apnea-hypopnea index >30) than the others: 71% versus 50.8% (P = 0.049). Cumulative time of SPO2 below 90% (CT90%) was independently associated with DME after adjusting for confounding factors, whereas there was no difference between the oxygen desaturation index and minimum O2 saturation. CONCLUSION: Severe obstructive sleep apnea (apnea-hypopnea index >30) and parameters of nocturnal hypoxemia (cumulative time of SPO2 below 90%) are associated with DME.

SAFETY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX): The SAFODEX study. Incidence and Risk Factors of Ocular Hypertension.

PURPOSE: To analyze the incidence, risk factors, and time course of intraocular pressure elevation after intravitreal dexamethasone implant (Ozurdex). METHODS: The medical charts of 421 consecutive eyes (361 patients) receiving one or more Ozurdex implant between October 2010 and February 2015 were reviewed retrospectively. Ocular hypertension was defined as intraocular pressure of at least 25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were retinal vein occlusion (34%), diabetic macular edema (30%), postsurgical macular edema (17%), uveitis (14%), and other etiologies (5%). RESULTS: Among 1,000 intravitreal injections, ocular hypertension was recorded for 28.5% of injected eyes over a mean follow-up period of 16.8 months (3-55). Intraocular pressure-lowering medication was required for 31% of eyes. Only three eyes with preexisting glaucoma required filtering surgery to manage postinjection intraocular pressure elevation. Early retreatment between the third and fourth month does not increase the risk of intraocular pressure elevation. Younger age, male sex, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy, and a history of retinal vein occlusion or uveitis were significant risk factors for ocular hypertension after dexamethasone implant injection (P < 0.05 for all the above). CONCLUSION: Episodes of ocular hypertension after Ozurdex implant were generally transient and successfully managed with topical treatment. An analysis of the risk factors may help to determine the risk-benefit ratio for individual patients treated with dexamethasone implants.

REAL-LIFE STUDY IN DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT: The Reldex Study.

PURPOSE: To evaluate the efficacy and safety of intravitreal implant of dexamethasone (Ozurdex) in diabetic macular edema in real-life practice. METHODS: In this bicentric retrospective study, the authors reviewed 128 eyes of 89 patients. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, time to retreatment, and incidence of adverse effects. Linear mixed-effects models were used to study changes in best-corrected visual acuity and central macular thickness over the 3-year follow-up. RESULTS: Best-corrected visual acuity increased by a mean of 3.6 letters at Month 2 (P = 0.005), 4.2 letters at Month 12 (P = 0.006), 5.3 at Month 24 (P = 0.007), and 9.5 letters at Month 36 (P = 0.023). The proportion of eyes achieving at least a 15-letter improvement from baseline was 25.4% at Month 36. Central macular thickness decreased from 451 µm to 289 µm at Month 2 (P < 0.001), 370 µm at Month 12 (P < 0.001), 377 µm at Month 24 (P = 0.004), and 280 µm at Month 36 (P = 0.001). A mean of 3.6 injections were administered over the 3-year follow-up. Ten percent of eyes developed a transient increase in intraocular pressure (IOP ≥ 25 mmHg), and cataract was removed from 47% of phakic eyes. CONCLUSION: This large case series study showed favorable 3-year outcomes when using Ozurdex to treat diabetic macular edema. Intravitreal Ozurdex provides substantial long-term benefits in the treatment of diabetic macular edema in real-life.

PREVALENCE OF RETICULAR PSEUDODRUSEN IN AGE-RELATED MACULAR DEGENERATION USING MULTIMODAL IMAGING.

PURPOSE: To determine the rate of reticular pseudodrusen (RPD) in age-related macular degeneration using multimodal imaging, including color fundus photography, the blue channel image of fundus photography, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography, as well as to compare the sensitivities and specificities of these modalities for detecting RPD. METHODS: This prospective study included 243 eyes from 125 consecutive patients with age-related macular degeneration. They underwent fundus examination including color fundus photography, blue channel, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography in both eyes. To be considered as having RPD, eyes had to have reticular patterns on spectral domain optical coherence tomography in a large studied cube of 30° × 25° or on infrared reflectance with at least one other examination. RESULTS: The mean age of the 125 patients was 81.1 years (± 8.1). Eighty-six patients (68.8%) were diagnosed with RPD. Spectral domain optical coherence tomography, infrared reflectance, and multicolor imaging had the highest sensitivity (99.3, 84.6, and 87.1%, respectively) and specificity (100%). The color fundus photography, blue channel, and fundus autofluorescence had lower sensitivity to detect RPD. CONCLUSION: Reticular pseudodrusen is frequently associated with soft drusen in patients with age-related macular degeneration. As RPD may be rarely located only in the perifoveal area, spectral domain optical coherence tomography with a larger cube (30 × 25°) than that usually used (20 × 20°) had the highest sensitivity and specificity to detect RPD and is recommended to optimize the rate of detection.

Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

BACKGROUND: Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. AIMS: This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. METHODS: Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). RESULTS: Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. CONCLUSION: Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.

Oral histories of HIV/AIDS support group members, NGO workers and home-based carers in KwaZulu-Natal.

The purpose of this paper is to bring to the attention of the AIDS research community the existence of an oral history project known as the Memories of AIDS Project. The project focused on HIV/AIDS support group members, non-governmental organisation (NGO) workers and home-based carers in the Umgungundlovu (Pietermaritzburg) District Municipality, South Africa. The project was carried out by the Sinomlando Centre for Oral History and Memory Work, a research and community development centre of the University of KwaZulu-Natal, over a period of three years (2011-2013). Sixty-five individual oral history interviews of 1 to 4 hours duration and 11 focus group sessions were recorded, transcribed and translated from isiZulu into English when necessary. The life stories of community workers and support group members documented in the interviews show, on the part of the informants, a remarkable degree of agency and assertiveness in matters of sexuality, gender relations and religious beliefs. They found innovative ways of navigating through the conflicting claims of biomedicine, Christianity and African traditional religion. As much as the epidemic caused grief and suffering, it opened the door to new knowledge and new opportunities.

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats.

PURPOSE: Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits. METHODS: The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet. RESULTS: Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses. CONCLUSION: Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.

Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases.

BACKGROUND: To report the clinical features and outcomes of iris melanomas treated by proton beam therapy. MATERIALS AND METHODS: A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon, Department of Ophthalmology, in 36 patients treated by proton beam therapy for presumed (n = 29) and confirmed (n = 7) iris melanomas between July 1997 and October 2010. Ciliary body melanomas with iris involvement were excluded. The patients' mean age was 54.4 years (range, 22-82 years). The average tumor diameter was 3.8 mm (range, 2.5-8.0). The iridocorneal angle was invaded by the tumor in 47% of cases (n = 17), the ciliary body in 17% of cases (n = 6), and the sclera in 3% (n = 1). Raised intraocular pressure was present before treatment in 11.1 % of cases (n = 4). Tumor biopsy was performed in 19% of cases (n = 7). Four patients had undergone an initial incomplete surgical excision of tumor before radiotherapy. Surgical preparation of the eye with tantalum ring positioning had been performed in all cases 3-4 weeks before irradiation. The prescribed dose was 60 Cobalt Gray Equivalent (CGE) of proton beam radiotherapy delivered in four fractions on four consecutive days. RESULTS: The median follow-up was 50 months (mean 60.5, range 15-136). One patient (2.7%) was lost to follow-up. None of the patients showed tumor progression, local recurrence, or metastasis. None of the patients required secondary enucleation. Cataract was developed in 62% of patients, glaucoma in two cases (6%) after irradiation, and hyphema with the aggravation of pre-existing glaucoma in one patient. No patients developed neovascular glaucoma. CONCLUSIONS: Proton beam therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable rate of complications. Longer follow-up studies on a larger series is necessary to consolidate these results.

Efficacy and Safety of Fluocinolone Acetonide Implant in Diabetic Macular Edema: Practical Guidelines from Reference Center.

Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.

Polyunsaturated fatty acids prevent myosteatosis and lipotoxicity.

Myosteatosis occurs in response to excess circulating fatty acids and is associated with muscle dysfunction. This study aimed to characterize the sequence of events of lipid-induced toxicity within muscle cells and the role of polyunsaturated fatty acids (PUFA) as potential preventive factors. Myosteatosis was induced in C2C12 myotubes exposed to palmitic acid (PAL 500µM). Furthermore, cells were co-incubated with PUFA (α-linolenic acid = ALA, Eicosapentaenoic acid = EPA, Docosahexaenoic acid = DHA; Arachidonic acid = ARA) over a period of 48 h. Cell viability, morphology, and measures of lipid and protein metabolism were assessed at 6, 12, 24, and 48 h. We observed that myotube integrity was rapidly and progressively disrupted by PAL treatment after 12 h, ultimately leading to cell death (41.7% cell survival at 48 h, p < .05). Cell death did not occur in cells exposed to PAL+ARA and PAL+DHA. After 6 h of PAL treatment, an accumulation of large lipid droplets was observed within the cell (6 folds, p < .05). This was associated with an increase in ceramides (CER x3 fold change) and diacylglycerol (DAG x150 fold change) contents (p < .05). At the same time, insulin was no longer able to stimulate protein synthesis (p < .05) nor leverage autophagic flux (p < .05). DHA and ARA were able to completely reverse the defect in protein synthesis and partially modulate the accumulation of CER and DAG. These findings present new and intriguing research avenues in the field of muscle metabolism and nutrition, particularly in the context of aging, chronic muscle disorders, and insulin resistance.