Visual acuity and vision-related quality of life outcomes following cataract surgery in Ebola virus disease survivors.

Objectives: The objectives of this study were to assess relationships between vision-related quality of life (QoL) and visual acuity (VA) in Ebola virus disease (EVD) survivors after cataract surgery in the Ebola Viral Persistence in Ocular Tissues and Fluids (EVICT) Study. Materials and Methods: EVD survivors with undetectable Ebola virus (EBOV) ribonucleic acid in their aqueous humour were eligible to receive manual small-incision cataract surgery (MSICS). Among those that received surgery, assessments of VA and vision-related QoL were assessed pre-and post-cataract surgery. VA was converted from units on a tumbling 'E' chart to the logarithm of the minimal angle of resolution VA (logMAR VA). Vision-related QoL was assessed using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Linear regression was used to evaluate the associations between VA and vision-related QoL. P = 0.05 was considered statistically significant for all analyses. Results: Thirty-four EVD survivors underwent cataract surgery in the EVICT study. Before MSICS, the mean logMAR VA was 2.24 (standard deviation [SD]: 0.98), and the mean NEI-VFQ-25 composite score was 54 (SD: 15); however, there was no significant association between the pre-surgery measurements (average difference in VA/10 unit increase in NEI-VFQ-25: -0.04, 95% confidence interval (CI): -0.33-0.26, P = 0.80). There was a significant improvement in logMAR VA after MSICS (mean: 1.6, P < 0.001), but there was no significant change in the NEI-VFQ-25 composite (-0.87, 95% (CI): -10.32-8.59, P = 0.85). None of the subscales showed significant improvements (P > 0.12 for all); however, the magnitude of the mean change for distance activities (6.65), near activities (6.76), general vision (-7.69), social functioning (-9.13) and colour vision (13.33) met the criteria for a clinically meaningful difference (4-6). In the subset with paired measurements (n = 16), there were no significant association changes in logMAR VA and NEI VFQ-25 composite scores (P > 0.12 for all). Conclusion: Following cataract surgery, VA in EVD survivors improved, but these improvements were not reflected in NEI VFQ-25 composite scores or specific subscales; however, the small sample size limits generalizability absent more research. Differences in sociocultural context and activities that affect the QoL in resource-limited areas may contribute to the limitations seen with NEI VFQ-25. In addition, better eye dominance could contribute to any lack of association as NEI VFQ-25 evaluates vision as a whole. Further, assessment of factors contributing to improved QoL may help to define the impact of vision health in varied environments.

Longer-Term Anti-VEGF Therapy Outcomes in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Vein Occlusion-Related Macular Edema: Clinical Outcomes in 130 247 Eyes.

PURPOSE: The clinical practice visual acuity (VA) outcomes of anti-VEGF therapy for up to 5 years were assessed in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), branch retinal vein occlusion-related macular edema (BRVO-ME), and central retinal vein occlusion-related macular edema (CRVO-ME). DESIGN: A retrospective analysis was performed using the Vestrum Health Retina Database. PARTICIPANTS: Treatment-naive patients with nAMD, DME, BRVO-ME, or CRVO-ME who received anti-VEGF injections between 2014 and 2019 and had follow-up data for ≥12 months. METHODS: Data on age, sex, the number of anti-VEGF treatments, and VA were analyzed. MAIN OUTCOME MEASURES: Mean VA change up to 3 years (BRVO-ME and CRVO-ME) and 5 years (nAMD and DME). RESULTS: At 1, 3, and 5 years, in 67 666, 21 305, and 5208 eyes with nAMD, after a mean of 7.6, 19.5, and 32 injections, there was a mean change of +3.1, -0.2, and -2.2 letters, respectively. At 1, 3, and 5 years, in 40 832, 7728, and 1192 eyes with DME, after a mean of 6.2, 15.4, and 26.0 injections, there was a mean change of +4.7, +3.3, and +3.1 letters, respectively. At 1 and 3 years, in 12 451 and 3027 eyes with BRVO-ME, after a mean of 7.1 and 18.2 injections, there was a mean change of +9.5 and +7.7 letters, respectively. At 1 and 3 years, in 9298 and 2264 eyes with CRVO-ME, after a mean of 7.3 and 18.8 injections, there was a mean change of +8.3 and +6.0 letters, respectively (P < 0.01 for all VA changes of > 1 letter). In all 4 conditions, the mean VA increased with the mean number of anti-VEGF injections, eyes with a baseline VA of 20/40 or better tended to lose VA, and eyes with progressively worse baseline VA experienced a progressively greater VA gain at 3 years. CONCLUSIONS: In practice, patients with nAMD, DME, BRVO-ME, and CRVO-ME showed limited visual outcomes, with patients with nAMD tending to lose VA at 3 and 5 years. Across all 4 disorders, the mean change in VA correlated with treatment intensity at 1, 3, and 5 years. Patients with better baseline VA are more vulnerable to vision loss.

Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using in vivo imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier.

Suprachoroidal Triamcinolone Acetonide for Retinal Vein Occlusion: Results of the Tanzanite Study.

PURPOSE: To compare the safety and efficacy of treatment with suprachoroidal triamcinolone acetonide (CLS-TA) plus intravitreal aflibercept vs. treatment with aflibercept alone in patients with macular edema due to retinal vein occlusion (RVO). DESIGN: Randomized masked controlled clinical trial. SUBJECTS: Forty-six patients with RVO. METHODS: Subjects were randomized 1:1 to suprachoroidal injection of CLS-TA plus intravitreal aflibercept (combination arm) or sham suprachoroidal injection plus aflibercept (aflibercept arm), followed by aflibercept as needed at months 1, 2, and 3 in each arm. MAIN OUTCOME MEASURES: The primary efficacy end point was the number of protocol-required aflibercept re-treatments through month 3. Secondary outcomes included mean improvement from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and the percentage of participants with CST ≤310 µm at each time point. RESULTS: The number of re-treatments were reduced in the combination arm compared with that in the aflibercept arm (23 vs. 9; -61%; P = 0.013) and the percentage of participants requiring no re-treatments was increased (78% vs. 30%; P = 0.003). The mean improvement from baseline BCVA letter score in combination vs. that in the aflibercept arms was 16.1 vs. 11.4 (P = 0.20) at month 1, 20.4 vs. 11.9 (P = 0.04) at month 2, and 18.9 vs. 11.3 (P = 0.09) at month 3. The mean baseline CST in the combination arm (731.1 µm) decreased into the normal range at month 1 (284.7 µm) and remained there at months 2 and 3 (272.4 µm and 285.4 µm). The mean baseline CST (727.5 µm) in the aflibercept arm decreased to 322.8 µm at month 1 and increased at months 2 and 3 (383.4 µm and 384.6 µm). Edema resolution (CST ≤ 310 µm) occurred in 87.0%, 87.0%, and 78.3% of participants in the combination arm at months 1, 2, and 3, respectively, vs. 56.5%, 47.8%, and 47.8% of participants in the aflibercept arm. In the combination arm, 1 participant had cataract progression and 4 (2 with preexistent glaucoma) had increased intraocular pressure that was controlled with topical medication. CONCLUSIONS: Combination intravitreal aflibercept and suprachoroidal CLS-TA is well tolerated and significantly reduces the need for additional intravitreal aflibercept injections over a 3-month period in patients with RVO. Preliminary evidence suggests that combination therapy may sustain edema resolution and improve visual outcomes.

Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine.

BACKGROUND: This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine. METHODS: Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom. RESULTS: A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom (p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg (p < .001) and nominally significant for 100 mg and 10 mg (p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose. CONCLUSIONS: MK-3207 was effective and generally well tolerated in the acute treatment of migraine.

Attitudes regarding the etiology and treatment of depression in Parkinson's disease: a qualitative study.

Depression in Parkinson's disease (dPD) remains under recognized and under treated. As patients' beliefs may impact the reporting and treatment of depression, this study assessed the opinions of 38 dPD patients, approximately half with a self-reported poor response to antidepressant treatment, regarding the etiology and treatment of their depression using a semi-structured, audio-taped, qualitative interview. About half of the participants listed PD itself as a primary cause for their depressive symptoms, with most in this group citing psychosocial factors rather than PD-related neurobiological factors. Antidepressant therapy, psychotherapy, and self-initiated approaches were noted as preferred treatments for dPD. Many had concerns about antidepressant therapy, listing side-effects and medication dependency most frequently. About half raised concerns about psychotherapy with trust/discomfort, stigma, and transportation issues most frequently mentioned. This preliminary study suggests that many PD patients with clinically significant depressive symptoms attribute their depression to psychosocial factors and endorse nonpharmacologic treatment approaches.

Escitalopram for major depression in Parkinson's disease: an open-label, flexible-dosage study.

Depression and antidepressant use are common in Parkinson's disease, but the benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this population has not been established. The authors treated 14 Parkinson's disease patients with major depression with escitalopram in an open-label study. Although treatment was well tolerated and correlated with a significant decrease in Inventory of Depressive Symptomatology score, response and remission rates were only 21% and 14%, respectively. However, half of the subjects met Clinical Global Impression-Improvement criteria for response. In Parkinson's disease, either SSRIs may have limited antidepressant effects, or the use of existing depression diagnostic and rating instruments may be problematic.

Daily affect in Parkinson disease is responsive to life events and motor symptoms.

OBJECTIVE: The aims of this study were to examine the daily affective experiences of patients with Parkinson disease (PD) and to determine their association with daily events and motor symptoms. Specifically, it was intended to test the hypothesis that PD, even in the absence of depression, is associated with anhedonia. METHOD: Nondepressed male subjects with PD (N=24) and a comparison group of healthy elderly males (N=23) completed daily affect rating scales and, for the patients with PD, a supplemental self-assessment questionnaire of PD-related symptoms for 4 consecutive weeks. The effect of daily events and PD-related symptoms on daily affect was examined using linear and logistic mixed regression models. RESULTS: Overall, patients with PD reported significantly less positive and more negative affect than healthy peers over time. There were similar, and expected, associations between negative events and affect in both groups. Although patients with PD reported far fewer positive events than control subjects, they reported as great an improvement in affect in response to them. Regarding self-reported PD-related symptoms, only increasing severity of core motor symptoms was independently associated with worse affect. CONCLUSIONS: Although the conclusions of this study are tempered by a comparison group that is not optimal, our results suggest that patients with PD do not demonstrate anhedonia in response to positive life events. The gross intergroup difference in daily events suggests the potential value of interventions that emphasize daily engagement in positive experiences to improve positive affective tone.