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Joseph M Coney,1 Jasmyne E McCoy,1 Samriddhi Buxy Sinha,2 Nina Sonbolian,2 Lujia Zhou,3 Thomas P Hull,1 Shawn A Lewis,1 David G Miller,1 Michael A Novak,1 Scott D Pendergast,1 Hang Pham,1 Sean M Platt,1 Llewelyn J Rao,1 Jerome P Schartman,1 Lawrence J Singerman,1 Richard Donkor,1 Margaret Fink,1 Ryan Zubricky,4 Helene Karcher2 1Retina Associates of Cleveland Inc, Beachwood, OH, USA; 2Novartis Pharma AG, Basel, Switzerland; 3KMK Consulting, Morristown, NJ, USA; 4Geisinger Eye Institute, Danville, PA, USACorrespondence: Joseph M Coney, Retina Associates of Cleveland Inc, 24075 Commerce Park, Beachwood, OH, 44122, USA, Tel +1 (216) 831-5700, Email jconey@retina-assoc.comObjective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.Methods: The overall study population comprised eyes that were given ≥ 1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥ 3 brolucizumab injections over ≥ 12 or ≥ 18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥ 2 brolucizumab injections and ≥ 1 other anti-VEGF over ≥ 12 or ≥ 18 months.Results: A total of 482 eyes received ≥ 1 brolucizumab injection during the study period. Mean VA changes from baseline were − 1.1± 15.1 letters (BRO cohort; n = 174) and 1.3± 13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0± 13.5 letters (BRO cohort; n = 95) and − 7.3± 17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9± 48.1 days (BRO cohort) and +11.1± 17.3 days (ALT cohort) at Month 12 and +36.3± 52.3 days (BRO cohort) and +14.0± 19.9 days (ALT cohort) at Month 18. Mean changes in CMT were − 35.2± 108.1 μm (BRO cohort) and − 31.5± 91.2 μm (ALT cohort) at Month 12 and − 38.9± 75.0 μm (BRO cohort) and − 9.0± 59.9 μm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.Keywords: alternating anti-VEGF treatments, brolucizumab, neovascular age-related macular degeneration, wet age-related macular degeneration, 12-month outcomes, 18-month outcomes

Countries across the world are experiencing syndemic health crises where infectious pathogens including COVID-19 interact with epidemics of communicable and non-communicable diseases. Combined with war, environmental instability and the effects of soaring inflation, a public health crisis has emerged requiring an integrated response. Increasingly, national public health institutes (NPHIs) are at the forefront of leading this, as demonstrated at the 2022 Annual Meeting of the International Association of National Public Health Institutes (IANPHI). These effects are particularly evident where conflict is exacerbating health crises in Ukraine and Somalia. In Ukraine, medical and public health workers have been killed and infrastructure destroyed, which require major efforts to rebuild to international standards. In Somalia, these crises are magnified by the effects of climate change, leading to greater food insecurity, heat-related deaths and famine. National public health institutes are crucial in these contexts and many others to support integrated political responses where health challenges span local, national and international levels and involve multiple stakeholders. This can be seen in strengthening of Integrated Disease Surveillance and work towards the Sustainable Development Goals. National public health institutes also provide integration through the international system, working jointly to build national capacities to deliver essential public health functions. In this context, the 2022 IANPHI Annual meeting agreed the Stockholm Statement, highlighting the role that NPHIs play in tackling the causes and effects of interconnected global and local challenges to public health. This represents an important step in addressing complex health crises and syndemics which require whole-of-society responses, with NPHIs uniquely placed to work across sectors and provide system leadership in response., (© 2023 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

Background: On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern.", Methods: By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa--Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14., Results: The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0 ) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total., Conclusions: These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Objective: To assess the prevalence of herpesvirus DNA in ocular fluids obtained from healthy patients undergoing vitreoretinal surgery., Background: Polymerase chain reaction (PCR) has been used to detect herpesvirus DNA in patients with acute retinal necrosis and cytomegalovirus retinitis. Little is known regarding the prevalence of detectable herpesvirus DNA in ocular fluids collected from healthy seropositive patients with no clinical evidence of viral retinitis., Methods: Seventy-five intraocular specimens (35 aqueous and 40 vitreous samples) were collected from 75 patients undergoing scleral buckling or vitrectomy. Using a PCR-based assay, the authors tested each specimen for the presence of herpesvirus genome DNA with primers specific for cytomegalovirus, Epstein-Barr virus, herpes simplex virus types 1 and 2, and varicella zoster virus. Serologic testing for immunoglobulin G (IgG) and IgM levels corresponding to each of the herpesviruses was also performed., Results: Of the 75 samples tested, none was found to harbor herpesvirus DNA. The assay did not give false-positive results in patients with active intraocular inflammation. The sensitivity of the assay was 0.08 infection-forming units for cytomegalovirus, 0.6 tissue culture infectious doses for herpes simplex virus, 0.5 infected-cell equivalents for Epstein-Barr virus, and 0.03 focus-forming units for varicella zoster virus. The percentage of patients with positive herpesvirus serology ranged from 86% to 100% and was consistent with rates observed in the general population., Conclusions: The prevalence of herpesvirus DNA detectable by PCR techniques in ocular fluids appears to be quite low despite the high proportion of patients who tested positive for herpesvirus antibodies. Therefore, a positive result obtained in a patient presenting with vitreoretinal inflammation should be regarded as significant.

Purpose: We report the results of pars plana vitrectomy for chronic pseudophakic cystoid macular edema unresponsive to medical treatment., Methods: Retrospective analysis of 23 consecutive eyes of 23 patients with chronic pseudophakic cystoid macular edema was performed. Eyes with vitreous incarceration into the cataract wound or vitreous-cornea contact were excluded from the study. Preoperatively, all eyes had cystoid macular edema confirmed on fluorescein angiography and were unresponsive to medical treatment. Pars plana vitrectomy was performed using standard techniques and vitreous adhesions to the iris, intraocular lens, or both were lysed if present., Results: The mean interval between cataract surgery and vitrectomy was 32.3+/-30.9 months (median, 20 months; range, 3 to 110 months). The vitreous was adherent to the iris or intraocular lens in 12 eyes (52.2%) and was present in the anterior chamber with no evidence of adhesions in seven eyes (30.4%). In four eyes (17.4%) the vitreous was posterior to the iris plane with no adhesions to anterior segment structures. The median preoperative best-corrected visual acuity was 20/200, and the median final postoperative best-corrected visual acuity was 20/60 (P<.0001) after a mean follow-up of 30.2+/-31.2 months (median, 14 months; range, 2 to 109 months). Final best-corrected visual acuity improved by a mean of 3.3+/-2.6 Snellen lines, with a median percent change of 70% (mean, 57.3%; range, 0% to 99%). In all 23 eyes the cystoid macular edema resolved postoperatively by biomicroscopic examination in a mean period of 3.3 months (median, 2 months; range, 1 to 12 months)., Conclusions: In pseudophakic eyes with chronic cystoid macular edema unresponsive to medical treatment, vitrectomy resulted in resolution of the cystoid macular edema with improved visual acuity in some cases. Clinical improvement may occur in eyes with no apparent vitreous disturbance.

Multicentric melanomas in the same eye are rare, with few cases substantiated by histology and serial sectioning. We report a patient with two documented choroidal malignant melanomas in one eye. The initial tumor spontaneously decreased in size for over 2 years before a second tumor appeared in a noncontiguous location in the same eye. After enucleation, serial sections showed that the two lesions were independent choroidal melanomas. We review the literature regarding multiple, independent intraocular choroidal malignant melanomas.

Purpose: Posterior lens fragments after phacoemulsification can be a serious complication of cataract surgery. This study is designed to evaluate the clinical features of eyes after pars plana vitrectomy has been performed to remove posteriorly dislocated lens fragments after phacoemulsification., Methods: The authors performed a retrospective chart review of 126 consecutive eyes of 126 patients with dislocated lens fragments after phacoemulsification, managed with pars plana vitrectomy at Associated Retinal Consultants of Michigan. These eyes were operated on from January 1986 through January 1996., Results: The relation of the intervals between cataract surgery and vitrectomy to various postoperative clinical parameters was studied. Clinical features at presentation included elevated intraocular pressure (IOP over 25 mmHg) in 52.4% of the eyes, uveitis in 69.6%, and corneal edema in 50.8%. Initial visual acuity was 20/400 or worse in 73.8% of the eyes. The mean preoperative visual acuity was 20/278 (median, 20/400), whereas the mean final visual acuity was 20/40 (median, 20/50) after a mean follow-up of 18.9 months. Retinal detachments were found in 20 eyes: 7 before vitrectomy and 13 during or after it. After surgery, 44% of eyes achieved a final visual acuity of 20/40 or better and 90% were 20/400 or better. The distribution of best-corrected final visual acuities among the eyes showed statistically significant differences based on the type of intraocular lens (IOL) used, with posterior chamber IOL greater than anterior chamber IOL, and anterior chamber IOL greater than aphakia. Reasons for a poor visual outcome included persistent corneal edema (four eyes), retinal detachment (two eyes), central retinal vein occlusion (two eyes), age-related macular degeneration (two eyes) glaucoma (one year), and endophthalmitis (one eye)., Conclusions: There were no statistically significant differences between early (< 7 days) and delayed (8 days or more) vitrectomy when increased IOP, corneal edema, choroidal effusions, cystoid macular edema, and visual acuity were analyzed. The use of vitrectomy to remove posteriorly dislocated lens fragments has been shown to be an effective treatment method that significantly reduces the inflammatory response and hastens visual recovery.

Background: Retinopathy of prematurity (ROP) is a retinal vascular disease occurring in infants with short gestational age and low birth weight and can lead to retinal detachment (ROP stages 4 and 5). X-linked familial exudative vitreoretinopathy is phenotypically similar to ROP and has been associated with mutations in the Norrie disease (ND) gene in some cases., Objective: To determine if similar mutations in the ND gene may play a role in the development of advanced ROP., Methods: Clinical examination and molecular genetic analysis were performed on 16 children, including 2 dizygotic and 1 monozygotic twin pairs, and their parents from 13 families., Results: Sequencing of the amplified products revealed missense mutations (R121W and L108P) in the third exon of the ND gene in 4 patients. These mutations were not present in an unaffected premature twin, 2 children with regressed stage 3 ROP, the parents, or in 50 unrelated healthy control subjects., Conclusion: These findings suggest that mutations in the ND gene may play a role in the development of severe ROP in premature infants.

Background: Cutis marmorata telangiectatica congenita is a rare, cutaneous, reticulated, vascular anomaly characterized by congenital persistent cutis marmorata, telangiectasis, and phlebectasis. While systemic abnormalities frequently are associated with cutis marmorata telangiectatica congenita, ophthalmic abnormalities are quite rare and include congenital glaucoma and congenital, bilateral, total retinal detachments with secondary glaucoma., Methods: The authors report a case of bilateral, tractional retinal detachments associated with peripheral fibrovascular proliferation simulating familial exudative vitreoretinopathy in a female child with cutis marmorata telangiectatica congenita. Molecular genetic analysis of the Norrie's disease gene was performed., Results: After vitrectomy, the posterior poles of both eyes were reattached successfully. No abnormalities of the Norrie's disease gene were identified., Conclusions: Bilateral exudative vitreoretinopathy is a rare ophthalmic manifestation associated with cutis marmorata telangiectatica congenita.

Background: Vitrectomy has been successfully used for treating idiopathic macular holes. Although macular hole surgery has been successful and is generally regarded as a safe procedure, various complications have been reported. The authors report eight patients with symptomatic peripheral visual field loss occurring after vitrectomy for macular holes., Methods: Over a 3-year period, vitrectomy with removal of the posterior cortical vitreous and fluid-gas exchange was performed on 50 eyes of 47 patients with idiopathic macular holes. Eight patients reported visual field loss postoperatively, and Goldmann visual fields were obtained. The clinical characteristics and outcomes of the group of patients with visual field loss were compared with the group of patients without visual field loss., Results: Postoperatively, significant peripheral visual field loss was documented in eight patients. The macular holes were anatomically closed in seven eyes (87.5%) of these patients compared with 37 (88.1%) of 42 eyes in the group of patients with no symptomatic visual field loss. The visual field loss was not associated with age, sex, macular hole stage, postoperative intraocular pressure, or history of hypertension or coronary artery disease. The etiology of visual field loss was unclear in six patients., Conclusion: Vitrectomy for idiopathic macular holes can result in significant peripheral visual field loss. The etiology of this complication usually is unknown.

Purpose: Our purpose was to evaluate the reproducibility of optic nerve head depth measurements using the Glaucoma-Scope., Materials and Methods: Optic nerve head topography was measured with the Glaucoma-Scope in 10 normal subjects and in 10 patients with glaucoma. Five separate readings were obtained by a single observer from one eye of each subject on the same day. Mean depth values were calculated for the overall disc, each quadrant, and areas overlying vessels at those points at which the change from baseline exceeded 50 mum. Similar calculations were made for actual depth measurements in regions of potential clinical interest, including the bottom of the cup, the temporal slope, the nasal disc, and a peripapillary region, as well as 15 randomly selected single points. Reproducibility of the depth values was determined by calculating standard deviations, coefficients of variation, and 95% confidence intervals in the five separate measurements., Results: The mean standard deviations in regions of potential clinical interest among the 20 subjects ranged from 3.98 mum to 14.09 mum, and the mean coefficient of variation ranged between 4.2% and 8.7%. The 95% confidence intervals for the total population ranged from 9.88 mum to 34.97 mum for the regions of interest and was 43 mum for the 15 random points. There was no statistically significant difference in reproducibility between the two groups of subjects., Conclusion: In this study the Glaucoma-Scope produced quantitative optic nerve head topographic measurements that were highly reproducible, within a tolerance of <50 mum.

Background: The morphologic features and clinical consequences of removing residual optic disc stalks during vitrectomy for complications of diabetic retinopathy have not been described., Methods: Twenty-four residual optic disc stalks that were surgically removed from eyes with proliferative diabetic retinopathy and dense nonclearing vitreous hemorrhage and/or traction retinal detachment were studied histologically using conventional hematoxylin and eosin staining as well as a modified Glees staining technique., Results: Histologic examination demonstrated that 79% of the specimens consisted of vascularized glial tissue with an infiltrate of mononuclear cells and 21% consisted of glial membranes devoid of vasculature. Axons were identified in 33% of all tissues studied. Intra-operative hemorrhage occurred in three eyes with strongly adherent optic disc stalks and was controlled with transient elevation of the intraocular pressure. The presence of axons in the removed optic disc stalks was not correlated with a decreased final postoperative visual acuity (median time to follow-up 21 months)., Conclusions: Residual optic disc stalks removed during vitrectomy for proliferative diabetic retinopathy frequently contained axons. The presence of axons does not portend an unfavorable postoperative visual outcome.