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Colin S Tan,1,2 Wei Kiong Ngo,1,2 Isaac W Chay,1,2 Dominic S Ting,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore; 3Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA, USACorrespondence: SriniVas R Sadda, Doheny Image Reading Center, Doheny Eye Institute, 3623, 1450 San Pablo Street, Los Angeles, CA, 90033, USA, Email sadda@usc.eduAbstract: Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.Keywords: neovascular AMD, anti-VEGF, retina, gene therapy

Aditya Verma,1,2 Tommaso Bacci,3,4 David Sarraf,5 K Bailey Freund,3,4 SriniVas R Sadda1,2 1Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3Vitreous Retina Macula Consultants of New York, New York, NY, USA; 4Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA; 5Stein Eye Institute, David Geffen School of Medicine at University of California, Los Angeles, CA, 90095, USACorrespondence: SriniVas R Sadda Email SSadda@doheny.orgAbstract: This review article summarizes the patho-anatomy of the vortex veins, the major drainage channels for the choroid, and describes the various pathways of diseases associated with vortex vein abnormalities. This report also details the technical advancements to image the vortex veins, such as ultra-widefield indocyanine green angiography, which are critical to elucidate the importance of the vortices in various retino-choroidal disorders. Future applications of these advanced imaging systems to better understand the role of the vortex veins in health and disease are also discussed.Keywords: choroid, optical coherence tomography angiography, pachychoroid disease, ultra-widefield imaging, vortex veins

Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV) is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT), the current treatment of choice is anti-vascular endothelial growth factor (VEGF) agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT). In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

PURPOSE: To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aβ42/tau ratios. METHODS: Swept-source OCTA scans were collected using the Zeiss PLEX Elite 9000 and analyzed on 23 cognitively healthy (CH) subjects who had previously undergone CSF analysis. Thirteen subjects had a pathological Aβ42/tau (PAT) ratio of

BACKGROUND: Peripapillary vitreous traction (PVT) occurring without any underlying eye disease has been contemplated as a distinct entity from nonarteritic ischemic optic neuropathy (NAION) for many years and is sometimes difficult to differentiate from classical NAION. We report 6 new cases to analyze the clinical features of PVT syndrome that would expand the clinical spectrum of anterior optic neuropathies. METHODS: Prospective case series. RESULTS: PVT syndrome seems to affect optic discs with a small area with a small cup-to-disc (C/D) ratio. The C/D ratio does not significantly increase in the chronic stage, as in NAION. Vitreous traction without detachment can either lead to mild retinal nerve fiber layer (RNFL) injury with attendant ganglion cell layer/inner plexiform layer (GCL/IPL) thinning in 29% or no injury at all in 71%. Eighty-six percent had good visual acuity (VA) and had no relative afferent pupillary defect (RAPD), whereas 14% had a transient RAPD; 71% had no color defect. Vitreous detachment after a period of severe and persistent traction can lead to more damage to the optic nerve head and RNFL that may look like NAION. Our hypothesized mechanically induced injury to the superficial optic nerve head may not lead to much visual impairment. In our study, no further therapeutic interventions were required. CONCLUSIONS: Based on our analysis of previously published cases and our own prospective case series of 6 patients, the PVT syndrome falls within the spectrum of anterior optic neuropathies, often affecting small optic discs with a small C/D ratio. Vitreous traction can lead to a partial or complete anterior optic neuropathy. The PVT syndrome may be a more anterior optic neuropathy distinct from classical NAION.

Elias Reichel,1 Glenn J Jaffe,2 Srinivas R Sadda,3 Stefanie Schuman,2 Amir H Hariri,3 Keegan Skidmore,1 Jake Duker1 1Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, 2Duke Eye Center, Duke Reading Center, Durham, NC, 3Department of Ophthalmology, Doheny Eye Centers, University of California, Los Angeles, CA, USA Purpose: The aims of this study were to determine the prevalence of vitreomacular adhesion (VMA) in a random sample of clinical patients at three US retina clinics and to assess comorbid retinal conditions, ocular diseases, prior treatment history, and other medical histories. Patients and methods: This observational, retrospective cohort study was based on patients from the Doheny Eye Centers, Duke Eye Center, and Tufts Medical Center who received a bilateral spectral domain optical coherence tomography (SD-OCT) scan (one scan/eye) for clinical evaluation with available medical records. The study had three phases: 1) collection of retrospective patient data; 2) review of OCT scans at a reading center to assess VMA and associated conditions; and 3) analyses and reporting of data on the prevalence of VMA, patient demographics, and comorbid conditions. Data were obtained from electronic health records and OCT grading forms. Outcome measures from bilateral SD-OCT scans and medical records included OCT evaluation of VMA and retinal comorbid conditions. Results: In 719 patients with 1,483 reviewable OCT scans, the prevalence of VMA was estimated at 14.74% (90% CI, 12.58%–16.92%). The prevalence of unilateral VMA was estimated at 12.39%, while bilateral VMA was 2.36%. In patients with VMA, 34 out of 123 eyes with VMA (27.64%) also had fovea deformed by vitreomacular traction. Macular hole (MH) was significantly more prevalent in VMA-diagnosed eyes versus non-VMA-diagnosed eyes (6.5% versus 1.9%; P=0.02). There was a significantly higher incidence of full-thickness MH (P=0.008), operculum/flaps (P

Anthropogenic Pressure and Landscape Dynamics in Semi-arid Rural Areas: the Case of Tibiri Commune, Maradi (Niger). In the Sahel (West Africa), climatic and socio-economic factors are the main causes of the current landscape structure. In this context, this study aimed to determine the influence of human activities on the dynamics of a semi-arid landscape by analyzing land use in the Tibiri Commune. To do this, we analyzed the changing trends at various spatial and temporal scales as well as the processes behing this landscape dynamics. The mapping approach and the application of landscape ecology principles between 1972 and 2010 revealed a continuous transformation of Tibiri commune landscape through different processes. The most dominant transformations are fragmentation and suppression. These are highly related to the agriculture (rainfed and irrigated crops) intensification and the urbanization which impact natural formations (savannas) and grazing areas (fallow/pasture mosaic). This land tendency to land saturation should lead in long run to full landscape anthropisation.

Michael A Singer,1 Colin S Tan,2 Krishna R Surapaneni,3 Srinivas R Sadda4 1Medical Center Ophthalmology Associates, San Antonio, TX, USA; 2National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 3University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 4Doheny Eye Institute, Los Angeles, CA, USA Introduction: Peripheral retinal ischemia not detectable by conventional fluorescein angiography has been proposed to be a driving force for rebound edema in retinal vein occlusions. In this report, we examine the treatment of peripheral retinal ischemia with targeted retinal photocoagulation (TRP) to manage a patient’s rebound edema.Methods: To assess the extent of peripheral nonperfusion, an Optos 200Tx device was used. To target the treatment to peripheral ischemia areas, a Navilas Panretinal Laser was used.Results: A 64-year-old male with a central retinal vein occlusion and a visual acuity 20/300, and central macular thickness 318 µm presented with rubeosis. Angiography revealed extensive peripheral nonperfusion. Despite TRP to areas of irreversible ischemia, after 2 months, he continued show rubeosis and rebound edema. Additional TRP laser was repeatedly added more posteriorly to areas of reversible nonperfusion, resulting in eventual resolution of rubeosis and edema.Conclusion: In this study, we demonstrate the use of widefield imaging with targeted photocoagulation of peripheral ischemia to treat rebound edema, while preserving most peripheral vision. In order to treat rebound edema, extensive TRP, across reversible and nonreversible areas of ischemia, had to be performed – not just in areas of nonreversible peripheral ischemia. These areas need to be mapped during episodes of rebound edema, when ischemia is at its maximum. In this way, by doing the most TRP possible, the cycle of rebound edema can be broken. Keywords: macular edema, retinal vein occlusion

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohens Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.

The aim of this research is to prepare and study the kinetics effect of temperature and photochemical reactions of the hydroxamic acid derivatives of diethyl succinate through the interaction of alkyl halides and diethyl succinate in the presence of strong base. The transformation of ester to hydroxamic acid derivatives by the direct interaction between the ester hydroxyl amine hydrochloride in the presence of sodium hydroxide. Identification of the prepared compounds by determination of molecular weights and melting points . In addition to I.R and U.V spectroscopic absorption of the prepared compounds . Effect of temperature on the dissociation constant of hydroxamic acids derivatives in aqueous solutions. Ionic conductivity of these solutions were measured at different temperatures. It is found that the value of the dissociation constant of hydroxamic acid derivatives increase with temperature. The effect of radiation on the dissociation constant of hydroxamic acid derivatives through the preparation of series of solutions . Then these solutions were exposed to radiation at the wave length (λ=254nm), then the ionic conductivity was measured at different times and the dissociation constant (Ka, pK) was determined. It is found that dissociation constant increased with will time increment .

The aim of this research is the preparation of Poly (Methyl methacrylate –co- Methylacrylate) by a free radical initiating process for co-polymerization between methylmethacrylate and methyacrylate with amixing ratio (1:1), using benzoyl peroxide as an intiator at (70°C ) and(10%) ratio of conversion. Conversion of the ester group of the (CPMMA-MA) in to Hydroxamicacid was carried out by treatment of (CPMMA-MA) with hydroxylaminehydrochloride in alkaline medium at (pH=13) using Sodium Hydroxide. The poly hydroxamic acid was identified by (FT-IR) spectroscopy. Adsorption Capacity (qe) of the metal ions (Fe3+ ) and (Cu2+ ) using (PHA) was determined . Also the study showed that there was an effect of initial (pH ) and temperature on the adsorption capacity of (Fe3+ ) and (Cu2+ ) . Langmuir and Freundlich equation models were used to describe the equilibrium Sorption Isotherms , using different concentrations solution of (Fe3+ ) and (Cu2+ ) at pH=4 and 25°c by poly hydroxamic acid.

Pearse A Keane1, Srinivas R Sadda21NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USAAbstract: Retinal vein occlusions (RVOs) constitute the second most common cause of retinal vascular disease after diabetic retinopathy, with a prevalence of between 1% and 2% in persons older than 40 years of age. Despite the existence of numerous potential therapeutic options, none is entirely satisfactory, and many patients with RVO suffer irreversible visual loss. Fortunately however, the recent introduction of antivascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis®, Genentech, South San Francisco, CA) and bevacizumab (Avastin®, Genentech), offers a potentially new treatment approach for clinicians managing this disorder. The results of the BRAVO and CRUISE trials have provided the first definitive evidence for the efficacy and safety of ranibizumab in the treatment of RVO. As a result, ranibizumab has recently been approved by the US Food and Drug Administration for the treatment of RVO-associated macular edema. In this review, we provide a critical evaluation of clinical trial data for the safety and efficacy of ranibizumab, and address unresolved issues in the management of this disorder. Keywords: ranibizumab, retinal vein occlusion, vascular endothelial growth factor, macular edema

Age-related Macular Degeneration (AMD) is a major cause of irreversible vision loss in individuals over 55 years old in the United States. One of the late-stage manifestations of AMD, and a major cause of vision loss, is the development of exudative macular neovascularization (MNV). Optical Coherence Tomography (OCT) is the gold standard to identify fluid at different levels within the retina. The presence of fluid is considered the hallmark to define the presence of disease activity. Anti-vascular growth factor (anti-VEGF) injections can be used to treat exudative MNV. However, given the limitations of anti-VEGF treatment, as burdensome need for frequent visits and repeated injections to sustain efficacy, limited durability of the treatment, poor or no response, there is a great interest in detecting early biomarkers associated with a higher risk for AMD progression to exudative forms in order to optimize the design of early intervention clinical trials. The annotation of structural biomarkers on optical coherence tomography (OCT) B-scans is a laborious, complex and time-consuming process, and discrepancies between human graders can introduce variability into this assessment. To address this issue, a deep-learning model (SLIVER-net) was proposed, which could identify AMD biomarkers on structural OCT volumes with high precision and without human supervision. However, the validation was performed on a small dataset, and the true predictive power of these detected biomarkers in the context of a large cohort has not been evaluated. In this retrospective cohort study, we perform the largest-scale validation of these biomarkers to date. We also assess how these features combined with other EHR data (demographics, comorbidities, etc) affect and/or improve the prediction performance relative to known factors. Our hypothesis is that these biomarkers can be identified by a machine learning algorithm without human supervision, in a way that they preserve their predictive nature. The way we test this hypothesis is by building several machine learning models utilizing these machine-read biomarkers and assessing their added predictive power. We found that not only can we show that the machine-read OCT B-scan biomarkers are predictive of AMD progression, we also observe that our proposed combined OCT and EHR data-based algorithm outperforms the state-of-the-art solution in clinically relevant metrics and provides actionable information which has the potential to improve patient care. In addition, it provides a framework for automated large-scale processing of OCT volumes, making it possible to analyze vast archives without human supervision.

PurposeTo evaluate the feasibility of anterior segment optical coherence tomography (AS-OCT) for measuring anterior chamber (AC) cells in children with uveitis and to compare different AS-OCT acquisition modes.DesignValidity and reliability analysis.MethodsWe enrolled children younger than 18 years who had uveitis involving the anterior segment and children without eye disease as controls. All underwent clinical grading of AC cells. AC images of each eye were obtained using the Optovue Avanti RTVue XR AS-OCT. Two acquisition modes were used: a single cross-sectional line scan and an 8-line radial scan in an asterisk pattern. Two independent, masked graders counted cells manually on AS-OCT images. Rater agreement was assessed using intraclass correlation (ICC).ResultsIncluded were 30 children (59 eyes) with uveitis (median age 13.0 years, range 3-17 years) and 20 control children (40 eyes, median age 10.5 years, range 4-17 years). The number of eyes assigned each clinical grade of cells were as follows: none, 32 (54%); 0.5+, 12 (20.3%); 1+, 5 (8.5%); 2+, 8 (13.6%); 3+, 2 (3.4%). ICC of graders for line and radial scan protocols were 0.87 and 0.90. There was no significant difference between acquisition modes for pooled grader results (95% CI for difference: -0.04 to 0.14). ICC of cell counts between line and radial scan protocols was 0.85 (95% CI: 0.69-0.90). No control eyes had cells on AS-OCT images.ConclusionsQuantification of AC cell in children with uveitis is feasible with AS-OCT and has excellent reliability between different graders and acquisition modes.