Dexamethasone Implant under a Proactive Treatment Regimen in Clinical Setting: The ProDEX Study.

PURPOSE: To assess the effectiveness of switching intravitreal dexamethasone implants (DEX-implant) from pro re nata (PRN) treatment regimen to a proactive regimen in patients with macular edema of diverse etiologies. DESIGN: An observational, retrospective, uncontrolled, multicenter, national case series. PARTICIPANTS: Eighty-one eyes from 68 patients treated between October 2015 and June 2023 were included. METHODS: This study included consecutive eyes treated with DEX-implant who were switched from a PRN regimen to a proactive regimen for diabetic macular edema (DME), retinal vein occlusion (RVO), noninfectious uveitis macular edema (UME; including postsurgical macular edema), and radiation maculopathy (RM). MAIN OUTCOME MEASURES: The main outcome measures were change in the best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) at each visit. RESULTS: According to the etiology, DME represented 49.4% of eyes, UME 24.3%, RVO 21.0%, and RM 6.2%. The mean (standard deviation [SD]) duration of follow-up under the PRN and proactive regimens was 20.6 (13.3) and 14.2 (10.3) months, respectively. Switching from a PRN to a proactive regimen significantly improved mean (SD) BCVA by 3.7 (12.9) ETDRS letters (P = 0.01) with a mean (SD) decrease in CMT of 108.0 (151.4) µm (P < 0.001). The proportion of visits with significant anatomic recurrence (> 50 µm) also decreased from 40.1% to 6.0% after switching to a proactive regimen (P < 0.001). The number of DEX-implant injections significantly increased during the proactive treatment period (P < 0.001), but the change in the number of visits was not significantly different (P = 0.2). The proactive treatment period was not associated with a significant increase in IOP (P = 0.6). CONCLUSIONS: Switching to a proactive regimen in patients already treated with DEX-implant seems to significantly improve BCVA and CMT while maintaining stable IOP. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A new bio imagery user-friendly tool for automatic morphometry measurement on muscle cell cultures and histological sections.

TRUEFAD (TRUE Fiber Atrophy Distinction) is a bioimagery user-friendly tool developed to allow consistent and automatic measurement of myotube diameter in vitro, muscle fiber size and type using rodents and human muscle biopsies. This TRUEFAD package was set up to standardize and dynamize muscle research via easy-to-obtain images run on an open-source plugin for FIJI. We showed here both the robustness and the performance of our pipelines to correctly segment muscle cells and fibers. We evaluated our pipeline on real experiment image sets and showed consistent reliability across images and conditions. TRUEFAD development makes possible systematical and rapid screening of substances impacting muscle morphology for helping scientists focus on their hypothesis rather than image analysis.

Prevalence of comorbidities with the potential to increase the risk of nonadherence to topical ocular hypotensive medication in patients with open-angle glaucoma.

OBJECTIVE: To evaluate the prevalence of comorbidities that may limit or prevent adherence to topical ocular hypotensive therapy in patients with open-angle glaucoma (OAG). METHODS: The UK Clinical Practice Research Datalink (CPRD) database of primary and secondary care and prescription records was analyzed to identify patients with a first (index) diagnosis of OAG during 2016-2020. The primary care records of these patients were screened for diagnostic terms linked to prespecified (qualifying) comorbidities considered to have the potential to impact patients' ability to instill eye drops. The prevalence of each of 10 categories of qualifying comorbidity recorded within the period from 5 years before to 2 years after the index OAG diagnosis was analyzed. RESULTS: A total of 100,968 patients with OAG were included in the analysis. Among the patients in the OAG cohort, 13,962 (13.8%) were aged 40-54 years, 32,145 (31.8%) were aged 55-69 years, 42,042 (41.6%) were aged 70-84 years, and 12,819 (12.7%) were aged 85+ years. Within the OAG population, 82.7%, 14.6%, and 2.7% of patients had no category, one category, and two or more categories of qualifying comorbidity, respectively. Qualifying comorbidities were most common in older patients. The most prevalent qualifying comorbidities were categorized as degenerative, traumatic, or pathological central nervous system disorder disrupting cognitive function (5.2%), movement disorder (4.4%), and low vision (4.1%). The prevalence of arthropathies and injuries affecting upper limbs (including arthritis in the hands) was 2.4%. CONCLUSIONS: The presence of comorbidities should be considered when determining whether eye drops are suitable treatment for glaucoma. Neurodegenerative disease affecting cognition and memory, motor disease, and low vision are common comorbidities that may impact adherence to eye drops, and affected patients may benefit from non-drop treatment modalities.

European Glaucoma Society research priorities for glaucoma care.

BACKGROUND/AIMS: The goal of health research is to improve patients care and outcomes. Thus, it is essential that research addresses questions that are important to patients and clinicians. The aim of this study was to develop a list of priorities for glaucoma research involving stakeholders from different countries in Europe. METHODS: We used a three-phase method, including a two-round electronic Delphi survey and a workshop. The clinician and patient electronic surveys were conducted in parallel and independently. For phase I, the survey was distributed to patients from 27 European countries in 6 different languages, and to European Glaucoma Society members, ophthalmologists with expertise in glaucoma care, asking to name up to five research priorities. During phase II, participants were asked to rank the questions identified in phase I using a Likert scale. Phase III was a 1 day workshop with patients and clinicians. The purpose was to make decisions about the 10 most important research priorities using the top 20 priorities identified by patients and clinicians. RESULTS: In phase I, 308 patients and 150 clinicians were involved. In phase II, the highest-ranking priority for both patients and clinicians was 'treatments to restore vision'. In phase III, eight patients and four clinicians were involved. The top three priorities were 'treatments to stop sight loss', 'treatments to restore vision' and 'improved detection of worsening glaucoma'. CONCLUSION: We have developed a list of priorities for glaucoma research involving clinicians and patients from different European countries that will help guide research efforts and investment.

Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials.

PURPOSE: To evaluate the performance and safety of minimally invasive glaucoma surgery with a supraciliary drainage device (MINIject; iSTAR Medical, Wavre, Belgium) in primary open-angle glaucoma (POAG) as a stand-alone procedure. DESIGN: Meta-analysis. METHODS: At 11 sites in Colombia, France, Germany, India, Panama, and Spain, 82 patients were treated in 3 prospective, multicenter, interventional, nonrandomized trials (STAR-I, II, III). Data were pooled in a meta-analysis of up to 2 years of follow-up postimplantation. The main outcome measures were mean relative and absolute reduction in diurnal intraocular pressure (IOP) compared to baseline. Secondary outcomes included patients with IOP ≤18 mmHg, patients with IOP reduction ≥20%, number of IOP-lowering medications, adverse events, and endothelial cell density loss. RESULTS: At the 2-year follow-up (n = 66), mean IOP was reduced from 23.8 ± 3.3 mmHg at baseline to 14.4 ± 4.5 mmHg (-39.3%; P < 0.0001). An IOP reduction of ≥20% was achieved in 89.4% of patients, with 84.8% having an IOP ≤18 mmHg. IOP-lowering medications were reduced from a mean of 2.4 ± 1.1 to 1.4 ± 1.4 (P < 0.0001), with 37.9% of patients being medication-free at 2 years. Mean endothelial cell density loss at 2 years was 6.2 ± 9.1% compared to baseline and no patient had a loss >30%. CONCLUSIONS: This meta-analysis demonstrates the favorable safety and efficacy profile of a supraciliary device implanted in a stand-alone, ab-interno procedure in patients with mild-to-moderate POAG. The data demonstrate that MINIject is a safe and effective, bleb-free treatment option for patients requiring low target IOP up to 2 years.

Long-Term Outcomes of Birdshot Chorioretinopathy Treated with Corticosteroids: A Case Reports.

PURPOSE: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. METHODS: We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11). RESULTS: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. CONCLUSIONS: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Cost Utility and Value of Information Analysis of Femtosecond Laser-Assisted Cataract Surgery.

Importance: The efficacy and safety of femtosecond laser-assisted cataract surgery is well documented. An important requirement for decision makers is the evaluation of the cost-effectiveness of femtosecond laser-assisted cataract surgery (FLACS) over a sufficiently long horizon. Evaluating the cost-effectiveness of this treatment was a preplanned secondary objective of the Economic Evaluation of Femtosecond Laser Assisted Cataract Surgery (FEMCAT) trial. Objective: To estimate the cost utility of FLACS compared with phacoemulsification cataract surgery (PCS) on a 12-month time horizon. Design, Setting, and Participants: This multicenter randomized clinical trial compared FLACS with PCS in parallel groups. All FLACS procedures were performed using the CATALYS precision system. Participants were recruited and treated in ambulatory surgery settings in 5 university-hospital centers in France. All consecutive patients eligible for a unilateral or bilateral cataract surgery 22 years or older with written informed consent were included. Data were collected from October 2013 to October 2018, and data were analyzed from January 2020 to June 2022. Interventions: FLACS or PCS. Main Outcomes and Measures: Utility was measured through the Health Utility Index questionnaire. Costs of cataract surgery were estimated by microcosting. All inpatient and outpatient costs were collected from the French National Health Data System. Results: Of 870 randomized patients, 543 (62.4%) were female, and the mean (SD) age at surgery was 72.3 (8.6) years. A total of 440 patients were randomized to receive FLACS and 430 to receive PCS; the rate of bilateral surgery was 63.3% (551 of 870). The mean (SD) costs of cataract surgery were €1124.0 (€162.2; US $1235) for FLACS and €565.5 (€61.4; US $621) for PCS. The total mean (SD) cost of care at 12 months was €7085 (€6700; US $7787) in participants treated with FLACS and €6502 (€7323; US $7146) in participants treated with PCS. FLACS yielded a mean (SD) of 0.788 (0.009) quality-adjusted life-years (QALYs), and PCS yielded 0.792 (0.009) QALYs. The difference in mean costs was €545.9 (95% CI, -434.1 to 1525.8; US $600), and the difference in QALYs was -0.004 (95% CI, -0.028 to 0.021). The incremental cost-effectiveness ratio (ICER) was -€136 476 (US $150 000) per QALY. The cost-effectiveness probability of FLACS compared with PCS was 15.7% for a cost-effectiveness threshold of €30 000 (US $32 973) per QALY. At this threshold, the expected value of perfect information was €246 139 079 (US $270 530 231). Conclusions and Relevance: The ICER of FLACS compared with PCS was not within the $50 000 to $100 000 per QALY range frequently cited as cost-effective. Additional research and development on FLACS is needed to improve its effectiveness and lower its price. Trial Registration: ClinicalTrials.gov Identifier: NCT01982006.

Focal Photocoagulation as an Adjunctive Therapy to Reduce the Burden of Intravitreal Injections in Macula Edema Patients, the LyoMAC2 Study.

AIM: To assess the efficacy of focal photocoagulation of capillary macroaneurysms (CMA) to reduce the burden of intravitreal injections (IVI) in patients with macular edema (ME). MATERIALS AND METHODS: Retrospective multicenter study in patients with diabetic ME or ME secondary to retinal vein occlusion (ME-RVO). CMA associated with ME were selectively photocoagulated. Patients were followed for one year after photocoagulation. RESULTS: 93 eyes of 76 patients were included in this study. At 6 months after the laser (n = 93), there was a significant decrease in mean macular thickness (from 354 µm to 314 µm, p < 0.001) and in mean IVI number (from 2.52 to 1.52 at 6 months, p < 0.001). The mean BCVA remained stable (0.32 and 0.31 logMAR at baseline and 6 months, p = 0.95). At 12 months (n = 81/93), there was a significant decrease in mean macular thickness (from 354 µm to 314 µm, p < 0.001) and in mean IVI number (from 4.44 to 2.95 at 12 months, p < 0.001), while the mean BCVA remained stable (0.32 and 0.30 logMAR at baseline and 12 months, p = 0.16). CONCLUSION: Focal laser photocoagulation of CMA seems to be effective and safe for reducing the burden of IVI in patients with ME. Their screening during the follow-up should be considered closely.

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.

XEN® 63 gel stent to treat a refractory uveitic glaucoma: A case report.

PURPOSE: To describe the effectiveness of the XEN® 63 gel stent in a refractory uveitic glaucoma after failure of an Ahmed Glaucoma Valve. CASE DESCRIPTION: We report the case of a 54-year-old man with a history of uveitic glaucoma on his left eye due to Fuchs heterochromic iridocyclitis and neovascular glaucoma after a central retinal vein occlusion. Pre-operative intraocular pressure was 30 mmHg despite a QD (once-daily) dosed bimatoprost 0.3 mg and timolol 5 mg topical medication. At week 1, the eye exam showed an intraocular pressure of 6 mmHg with a well-formed bleb, a very mild hyphema and a localized choroidal detachment. At month 1, intraocular pressure was 14 mmHg with a formed bleb. Both hyphema and choroidal detachments had resolved. After a year, intraocular pressure was 16 mmHg without any medication and the bleb was still well-formed. CONCLUSION: The XEN® 63 gel stent provides a good intraocular pressure reduction and can be an efficient alternative for tube and filtration surgery in refractory glaucoma. Its long-term effectiveness needs to be evaluated.

Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle: role in sarcopenia.

Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.

Evaluation of the time required to complete a cataract training program on EyeSi surgical simulator during the first-year residency.

PURPOSE: To evaluate the time required to complete a cataract training program for first-year ophthalmology residents using the EyeSi simulator. In addition, evaluate whether the simulator improves virtual performance of cataract surgery during the program. METHODS: We prospectively included first-year ophthalmology residents who had no experience of cataract surgery. The EyeSi simulator was used, and residents were able to follow the cataract training program, including course A (the easiest) through to course D (the hardest). In course B and above, a "cataract challenge" is proposed to the trainee every hour of simulation. RESULTS: A total of 24 participants were included in the study. During the study period, the mean (SD) total time spent on the surgical simulator was 815.6 (174.7) minutes. All the participants completed courses A and B within a mean (SD) of 366.7 (108.0) minutes. A total of 22 residents (91.7%) residents completed course C, and 5 (20.8%) course D. The mean (SD) best score on cataract challenge was 445.6/500 (40.2; range: 330-493) and was obtained in a mean (SD) 7.6 (2.6) attempts. All the residents obtained a score ≥ 60%. The best score in cataract challenge was not correlated to the time spent to achieve courses A and B (r = -0.37, p = 0.0726). CONCLUSIONS: The time required to complete a basic cataract training program is possible during the first-year residency. The scores obtained in the cataract challenge also increased during the training program and should lead to better surgery skills in these young ophthalmologists.

Real-Life Value of the Odysight® Application in At-Home Screening for Exudative Recurrence of Macular Edema.

Background: The aim of this study was to describe the value of the Odysight® application in addition to a classical follow-up regimen in the detection of exudative recurrences in patients with macular edema. Methods: We conducted an observational, multicenter, retrospective study. The Odysight® application includes a visual acuity (VA) test that can lead to alerts in case of a drop of >5 VA letters on two successive tests. The efficacy of the alerts in detecting exudative recurrence was studied. Results: A total of 149 eyes of 123 patients were included. The sensitivity of alerts for the detection of recurrence was 30.8% (95% CI [17.6; 44.0]) and its specificity was 83.7% (95% CI [73.2; 94.3]. A better baseline VA was found to be significantly associated with a better retention of the application (OR = 0.05, 95% CI [0.002; 0.62]; p = 0.045). Of the 12/39 alerts that detected a recurrence, eight (20.5% of all alerts) resulted in the scheduling or advancement of an intravitreal injection. Conclusions: In the present study, the sensitivity and positive predictive value of the Odysight® application seems low but its use in addition to the usual follow-up of the patient can detect, in certain cases, an early recurrence and thus allow an anticipated readjustment of the treatment.

Intra-Ocular Pressure Response to Dexamethasone Implant Injections in Patients with a History of Filtering Surgery: The TRABEX Study.

Patients with both macular edemas, of various etiologies such as diabetes and glaucoma, may suffer serious loss of vision if either disease goes untreated. Where no effective alternative therapies are available, dexamethasone implant (DEX-I) injections may be the only choice of treatment, despite the risk of a possible increase in intraocular pressure (IOP) when using steroids. Although many studies have reported on IOP evolution in eyes treated with DEX-I, little is known specifically about eyes with a history of filtering surgery. The aim of this observational series was to evaluate the IOP response following DEX-I injection in eyes presenting conventional filtering surgeries or microinvasive glaucoma surgeries (MIGS). Twenty-five eyes were included in this study. A total of 64% of the eyes did not experience OHT during follow-up. Additional IOP-lowering therapy was needed for 32% of eyes, and 20% of eyes (all showing bleb fibrosis) required further filtering surgery: 50% of eyes in the MIGS group and 10.5% of eyes in the conventional filtering surgery group. A significant positive correlation was found between IOP at baseline and the maximum IOP throughout follow-ups after DEX-I (r = 0.45, p = 0.02). In conclusion, if DEX-I is used when there are no alternative therapies for treating macular edema, IOP in eyes with a history of filtering surgery is generally manageable. Those eyes which previously underwent conventional therapy with effective blebs obtained better IOP control after DEX-I injections and mostly did not require any additional IOP-lowering therapy or surgery.

Evaluation of the Correlation between Regional Retinal Ganglion Cell Damage and Visual Field Sensitivity in Patients with Advanced Glaucoma.

(1) Background: to investigate the correlation between structural (retinal ganglion cells and retinal nerve fibers) and functional alterations analyzed point-by-point in the central 10 degrees of the visual field of patients with advanced glaucoma using Humphrey 10-2 visual field tests. (2) Methods: Single-center prospective cohort study carried on from October 2018 to February 2019 at the Croix-Rousse hospital, Lyon, France. The primary outcome measure was the point-by-point correlation between retinal sensitivity (Humphrey 10-2) and retinal ganglion cell complex (GCC) thickness. (3) Results: 29 eyes of 27 patients were examined. Of these, 15 eyes had a mean deviation (MD) less than −20 dB. There were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the lower part of the visual field, with lower retinal sensitivity being associated with thicker GCC layers. There were no strong linear relationships or statistically significant correlations in the other regions of the visual field. For the patients with MD < −20 dB, there were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the superior nasal region. Retinal sensitivity was not correlated with retinal nerve fibre layer thickness. (4) Conclusions: In this study of patients with advanced glaucoma, GCC thickness was linearly associated with 10-2 visual field sensitivity in certain regions, negatively for patients with less-severe glaucoma. The initial thickening raises questions about the apoptosis mechanism, while the thinning observed in the most severe cases is consistent with the ganglion cell death identified on visual field tests.