Intellectual Property and the Politics of Public Good during COVID-19: Framing Law, Institutions, and Ideas during TRIPS Waiver Negotiations at the WTO.

CONTEXT: To facilitate the manufacturing of COVID-19 medical products, in October 2020 India and South Africa proposed a waiver of certain intellectual property (IP) provisions of a World Trade Organization (WTO) agreement. After nearly two years, a narrow waiver agreement that did little for vaccine access passed the ministerial despite the pandemic's impact on global trade, which the WTO is mandated to safeguard. METHODS: The authors conducted a content analysis of WTO legal texts, key-actor statements, media reporting, and the WTO's procedural framework to explore legal, institutional, and ideational explanations for the delay. FINDINGS: IP waivers are neither legally complex nor unprecedented within WTO law, yet these waiver negotiations exceeded their mandated 90-day negotiation period by approximately 18 months. Waiver opponents and supporters engaged in escalating strategic framing that justified and eventually secured political attention at head-of-state level, sidelining other pandemic solutions. The frames deployed discouraged consensus on a meaningful waiver, which ultimately favored the status quo that opponents preferred. WTO institutional design encouraged drawn-out negotiation while limiting legitimate players in the debate to trade ministers, empowering narrow interest group politics. CONCLUSIONS: Despite global political attention, the WTO process contributed little to emergency vaccine production, suggesting a pressing need for reforms aimed at more efficient and equitable multilateral processes.

Hyper-reflective vitreous spots in central retinal artery occlusion: An unusual finding in two cases.

PURPOSE: To present two consecutive cases of Central Retinal Artery Occlusion (CRAO) with unusual Optical Coherence Tomography (OCT) presentation of Hyperreflective Spots (HRS) in the posterior vitreous. CASE REPORT: The first patient was a 59 years-old male who developed CRAO in the post-operative period after aortic valve replacement. OCT scans revealed the presence of many HRS in the posterior vitreous, remarkably decreased in number at two months follow-up. The second patient was a 74-year-old male who developed CRAO after arterial chemoembolization for recurrent hepatocellular carcinoma. OCT scans showed again the presence of hyperreflective spots in the posterior vitreous and their reduction at two months follow-up with inner retinal atrophy as the final outcome in both cases. CONCLUSIONS: HRS in the posterior vitreous have been described in inflammatory eye conditions such as uveitis, diabetic macular edema, post cataract surgery, and considered a clinical sign of inflammation. To our knowledge, the combination of CRAO and HRS has not been previously reported. The number of HRS seems to decrease over time, suggesting a role for inflammatory response in the acute stage of CRAO. A similar pathogenic process is known to occur during cerebral ischemia, where the inflammatory response may exacerbate brain injury and post-ischemic damage.

Retinal vascular occlusion and SARS-CoV-2 vaccination.

PURPOSE: To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination. METHODS: In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging. RESULTS: Fifteen eyes of VO (14 patients) after COVID-19 vaccinations were identified. The median time between vaccination and symptoms onset was 14 days (range 7-42 days). The mean best-corrected visual acuity (BCVA) was 20/55 with a range of 20/20 to 20/200. Eleven of 15 eyes (73.3%) had visual acuity improvement after intravitreal treatment at 60-90 days (range, 45-105 days) from the presentation. Four of 5 cases without systemic risk factors for VO had a mean BCVA > 20/32 at presentation and > 20/25 at the latest evaluation. Between May 1 and October 31, 2021, a temporal association was found between the 15 reported cases and COVID-19 vaccination out of a total of 29 VO (p = 0.05). The incidence of VO was higher in the considered period compared to the equivalent 6-month period in 2019 (1.17% vs 0.52%, respectively; p = 0.0134). CONCLUSIONS: Retinal vascular occlusion with different grades of severity are reported in temporal association with COVID-19 vaccination. The exact pathogenic mechanism needs to be further studied. No certain causal relationship can be established from this case series.

Optical coherence tomography angiography for the measurement of optic disc: Macular relationship.

INTRODUCTION: Fundus photography is the gold standard for assessing ocular torsion over the last 30 years. However, it is not a precise and reproducible tool during clinical practice. Optical coherence tomography angiography is characterized by precise identification of the macula and the optic disc, and it could be an effective method to easily calculate the angle of ocular torsion, compared to fundus photography. The aim of this study was to show whether any difference in the measurement and the accuracy of the angle of torsion between the head of the optic nerve and the fovea was present. METHODS: This is a prospective single-, referral-center study conducted at the San Giuseppe Hospital in Milan on 80 eyes of 40 adult patients, included in a random-sample way. Exclusion criteria were non-cooperation, higher refractive errors of ±3 diopters, retinal and optic disc pathologies, and ocular movement disorders. RESULTS: Patients' mean age was 54.3 ± 16.3 (range: 22-83) years. The angle measured by the fundus camera was 7.78° ± 3.04°, while the angle measured by the angiography was 7.09° ± 3.08° (p = .035). The mean interocular difference was 1.54° ± 3.42° for fundus photography and 0.5° ± 4.71° for angiography (p = .013). CONCLUSION: Optical coherence tomography angiography is a very useful, fast, precise, reproducible, and reliable technique in cooperative subjects, not inferior to the fundus camera and less prone to human error.

Evaluating Medication Habits in Medical Mission Patients: A Cross-Sectional Study.

Background Short-term medical missions (STMMs) are a highly debated and largely understudied form of international volunteer work. With growing dedication to health care abroad, research evaluating their impact is crucial to ensure continued interventions are effective in improving medical care. STMM care varies in length, frequency, size, location, services offered, and country of origin and destination. This makes systematic evaluation of STMMs difficult. In addition, the transient nature of patient visits makes trending STMM's impact on long-term health outcomes complex. Despite intermittent availability, primary care missions offering pharmaceutical supplies have the unique opportunity to provide continued care to the community via free prescription supplies each visit. Given the challenges with measuring long-term outcomes in this population, it is unknown if these donated medications have any impact on patient health outcomes. As medication noncompliance is known to hinder health outcomes, our study chose to evaluate patient medication habits to see if these prescription supplies were being utilized appropriately. To our knowledge, no study has surveyed medical mission patients to explore their access and utilization of medication. Methods A cross-sectional study was conducted using a patient survey to identify risks and/or factors associated with medication noncompliance in patients visiting the medical mission, Waves of Health (WOH). For over 10 years, WOH has organized biannual seven-day trips to the Dominican Republic. The multi-question survey was translated into the native language, Spanish with Dominican dialect. Noncompliance was defined through the survey question "Did you run out of your prescription medication at all during the past year?" Spanish speaking participants, of both sexes and age ≥18 years old, who visited the mission clinic in November 2019 met inclusion for this study. Patients from Haiti or age <18 years old were excluded. Participation was voluntary. Survey items were dichotomized for univariate analysis to identify factors associated with running out of medication. To explore predictors of running out of medicine, we performed multivariate logistic regression analysis by ENTER method.  Results Of 127 patients, over half (58.3% [74]) reported running out of medication. Inadequate access to healthcare, daily medication use, and rationing personal medications were all significantly associated with running out of medicine. Frequency of WOH visits was not associated with running out of medication. Multivariate regression showed that being on daily medication and rationing personal medications were statistically significant predictors of running out of medicines. Access to healthcare, frequency of WOH visits, and WOH medication supply were not predictors of running out of medication. Conclusion  Mission interventions to improve medication practices should be explored due to the high number of patients who reported improper utilization of medication. In order to improve health outcomes in primary care settings, patients must play an active role in their care and understand the importance of taking their medication as prescribed for optimal disease management. Primary care STMMs may relieve short-term health concerns, but without proper utilization of chronic disease medications, it is unclear if STMMs role is impactful in long-term health outcomes.

Combination therapy with dexamethasone intravitreal implant and macular grid laser in patients with branch retinal vein occlusion.

PURPOSE: To test a combination of dexamethasone intravitreal implant with macular grid laser for macular edema in patients with branch retinal vein occlusion (BRVO). DESIGN: Prospective interventional, randomized, multicenter study. METHODS: Patients with macular edema secondary to BRVO underwent an Ozurdex intravitreal implant at baseline. After 1 month, patients were randomly assigned to 2 study groups. Patients in Group 1 were followed up monthly and retreated with Ozurdex implant whenever there was a recurrence of macular edema or a decrease in best-corrected visual acuity (BCVA). In Group 2 patients macular grid laser was performed between weeks 6 and 8. After that, patients were followed up and retreated as for Group 1. RESULTS: In Group 1 at 4 months, mean BCVA was 0.49 ± 0.35 logMAR and central retinal thickness (CRT) was 391 ± 172 µm; both improved significantly at 6 months, to 0.32 ± 0.29 logMAR and 322 ± 160 µm, respectively. In Group 2, CRT was reduced significantly to 291 ± 76 µm at 4 months, and BCVA improved to 0.25 ± 0.20 logMAR. At the final visit, BCVA was 0.18 ± 0.14 logMAR and mean CRT was 271 ± 44 µm. The number of Ozurdex implants at 4 months was 12 of 25 (48%) in Group 1 patients vs 3 of 25 (12%) in Group 2 patients (P = .012). At 6 months 3 of 25 patients (12%) in Group 1 vs 0 of 25 (0%) in Group 2 (P = .23) were retreated. CONCLUSIONS: The combination of Ozurdex implant and macular grid laser is synergistic in increasing BCVA and lengthening the time between injections.

Assessment of OCT measurements as prognostic factors in myopic macular hole surgery without foveoschisis.

BACKGROUND: To assess the role of Spectral Domain Optical Coherence Tomography (SD-OCT) measurements as prognostic factors in myopic macular hole (MMH) surgery. METHODS: In a retrospective cohort study, we evaluated 42 eyes of 42 patients (Spherical equivalent > -6.00 D) who underwent pars plana vitrectomy with internal limiting membrane peeling for MMH without foveoschisis. Statistical analysis was performed to correlate postoperative best corrected visual acuity (BCVA) with preoperative BCVA, age, degree of myopia and seven preoperative OCT measurements: macular hole (MH) base, MH minimum diameter, MH height, Hole Form Factor (HFF), Macular Hole Index (MHI), Diameter Hole Index (DHI) and Tractional Hole Index (THI). RESULTS: Primary and final anatomical success rate were 83.3% (35/42) and 90.5% (38/42), respectively. Four patients deferred reoperation and three underwent a second surgical approach to achieve MH closure. A posterior staphyloma was observed in 27 of 42 patients, and in three of them the MH was located in the apex of the staphyloma. Two of these three cases showed an open MH after the first surgery. Postoperative visual acuity improved in 22/42 (52.4%) patients, worsened in 7/42 (16.7%) and remained unchanged in 13/42 (30.9%). Only MH minimum diameter (P = 0.03) and HFF (P = 0.02) correlated significantly with postoperative BCVA. CONCLUSIONS: Minimum diameter and HFF are strongly correlated with postoperative visual outcomes in cases of MMH. Since analyzing MH configuration seems to improve the anatomical success rate after vitreous surgery in highly myopic patients, these parameters should be preoperatively evaluated by SD-OCT.

Intravitreal bevacizumab for macular complications from retinal arterial macroaneurysms.

PURPOSE: To evaluate the anatomic and functional results of the treatment with intravitreal bevacizumab in complicated retinal arterial macroaneurysm (RAM). DESIGN: A multicenter interventional, prospective, nonrandomized study. METHODS: Thirty-eight macroaneurysms of 37 patients with foveal complications were evaluated. All patients underwent a comprehensive ophthalmologic examination, fluorescein angiography (FA), and spectral-domain optical coherence tomography (SD OCT) examination. Each patient underwent 3 monthly injections of bevacizumab 1.25 mg/0.05 mL; 3 follow-up visits were planned at week 2, 6, and 12. RESULTS: Both best-corrected visual acuity (BCVA), expressed in logarithm of minimal angle of resolution (logMAR), and central retinal thickness (CRT) significantly improved during the follow-up visits (0.57 ± 0.21 vs 0.41 ± 0.15 vs 0.23 ± 0.13 vs 0.09 ± 0.10 and 520.38 ± 191.05 vs 396.24 ± 136.18 vs 283.86 ± 71.87 vs 214.84 ± 26.86, respectively, Friedman test P < .0001 for all variables). At 6 weeks of follow-up, FA showed complete closure of the RAM in 36 of 38 cases (94.7%). Four weeks following the third injection, the macular edema had completely resolved and hard exudates regressed slowly in 100% of patients. CONCLUSIONS: Intravitreal bevacizumab is an effective therapy for complicated RAM, quickly improving BCVA and CRT. Anti-vascular endothelial growth factor (VEGF) drugs might actively close the involved pathologically permeabilized retinal artery and normalize the vessel wall formation by localized inhibition of VEGF.

Double-vitrectomy for optic disc pit maculopathy.

BACKGROUND: The origin of the fluid and precise pathophysiology of optic pit maculopathy remain unclear. It has been suggested that submacular fluid originates either from vitreous or cerebrospinal fluid. We report a case of optic pit maculopathy which was unsuccessfully treated with vitrectomy and internal limiting membrane (ILM) peeling, and subsequently resolved with revision of vitrectomy and gas tamponade. METHODS: We report a case of optic disc pit maculopathy, well documented by spectral- domain optical coherence tomography, before and after pars plana vitrectomy with ILM peeling, and its revision with gas tamponade. RESULTS: After ILM peeling, there was no improvement either in visual acuity or in the tomographic aspect of the retina. A revision of the surgery was then needed and gas tamponade was performed, which resulted in a complete resolution of the optic pit maculopathy. CONCLUSION: The absence of improvement after ILM peeling during the first surgical procedure, accompanied by resolution of the clinical picture with gas tamponade during the second surgical procedure, sustained the hypothesis of a subarachnoidal origin of the fluid.

En face optical coherence tomography of inner retinal defects after internal limiting membrane peeling for idiopathic macular hole.

PURPOSE: To describe the appearance of inner retinal defects using en face spectral domain optical coherence tomography (SD-OCT) after idiopathic full-thickness macular hole (FTMH) surgery, referred to as concentric macular dark spots (CMDS). METHODS: In a retrospective cohort study, the authors evaluated 36 eyes of 36 patients with large idiopathic MH (>400 µm) who underwent standard three-port pars plana vitrectomy with internal limiting membrane (ILM) peeling. All patients were analyzed using B-scan and C-scan en face SD-OCT before and after surgery to determinate the OCT pattern of the retinal surface. RESULTS: Mean follow-up was 10 months (±8.45 SD; range, 3-30 months). Three months after surgery 36 of 36 eyes (100%) showed a CMDS appearance on en face SD-OCT images. Anatomic success rate was 100% (36/36 eyes) after a single surgical procedure. Once they were evident, these dark spots observed on the retinal surface were not progressive and remained stable over time. CONCLUSIONS: Inner retinal defects frequently occurred after idiopathic MH surgery when ILM was peeled. To the authors' knowledge, this feature has not been previously reported using an en face SD-OCT imaging, and it consisted of numerous CMDS in the same direction of the optic nerve fibers. All patients in the study showed this typical OCT pattern 3 months after surgery. Thus, the authors suggest that this is a helpful, noninvasive technique to assess complete ILM removal in FTMH surgery if CMDS appearance on the retinal surface is reported.

Spontaneous resolution of macular schisis in goldmann favre syndrome.

PURPOSE: The purpose of this study is to report a case of spontaneous flattening of macular schisis in a patient affected by Goldmann Favre syndrome (GFS). METHODS: A case report. RESULTS: A young boy affected by GFS came for a follow-up visit 10 years after the diagnosis. Spontaneous flattening of macular schisis, posterior hyaloid detachment, and visual acuity improvement from 20/200 to 20/80 were observed in the left eye. CONCLUSION: The observed spontaneous resolution of schisis in GFS, a rare inherited vitreoretinal dystrophy, suggests that an abnormality of the vitreoretinal interface could be the origin of macular schisis in this patient. This observation, reported for the first time to our knowledge, also leads to the hypothesis that the inconsistent presence of schisis in patients with GFS may not be a simple difference in phenotype but rather corresponds to different evolutional stages of the macula alterations in patients affected by GFS.

Spontaneous reattachment of the margins of a macular retinal pigment epithelium tear: optical coherence tomography documentation of a case.

PURPOSE: To document by optical coherence tomography (OCT) the reattachment of the margins of a retinal pigment epithelium (RPE) tear. METHODS: Single case report, documented by OCT scans, autofluorescence and fluorescein angiography. RESULTS: A 67-year-old male presented with a spontaneous RPE tear due to age-related macular degeneration in his right eye. Three months later we observed that the focal RPE tear had healed and there was a new intraretinal fluid, well documented by OCT imaging. CONCLUSIONS: OCT scans show the reattachment of the margins of an RPE tear healed by tissue remodelling, and illustrate how the disease can recur.