Lauren Ciulla

Bio: Lauren Ciulla is an academic researcher from Indiana University. The author has contributed to research in topics: Ranibizumab & Diabetic retinopathy. The author has an hindex of 4, co-authored 9 publications receiving 60 citations. Previous affiliations of Lauren Ciulla include Northwestern University.

Ranibizumab for diabetic macular edema refractory to multiple prior treatments.

Abstract: Purpose:Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sough

Vascular Endothelial Growth Factor Antagonists: Promising Players in the Treatment of Neovascular Age-Related Macular Degeneration.

Abstract: Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab monotherapy in a phase 1/2a trial. Sustained-release anti-VEGF therapies include the ranibizumab Port Delivery System (in phase 3 studies), GB-102 (Phase 2b), OTX-TKI (phase 1), and Durasert (preclinical). Suprachoroidal delivery of the tyrosine kinase inhibitor, axitinib, is in preclinical studies. Genetic therapies in phase 1 studies include RGX-314 and ADVM-022, which introduce a viral vector that modifies the retina's cellular apparatus to create an anti-VEGF biofactory, potentially serving as a one-time treatment. Further investigation is warranted for drugs and delivery systems that hope to advance visual outcomes and reduce treatment burden of nAMD.

Ranibizumab For Diabetic Macular Edema Refractory To Multiple Prior Treatments

Abstract: Purpose:Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sough

Circadian Rhythm and Glaucoma: What do We Know?

Abstract: Purpose The current understanding of circadian regulation disorders and their involvement in glaucoma pathophysiology are poorly understood, yet they may have a substantial impact on the onset and progression of glaucoma. Herein, we review and summarize all the available literature on circadian rhythm disorder and glaucoma to uncover the impact on glaucoma risk, and we highlight future research and potential novel targets for glaucoma management. Materials and methods A review of the relevant literature was performed through PubMed through August 1, 2019. Results Within a normal circadian rhythm, intraocular pressure (IOP) peaks at night, whereas blood pressure (BP) troughs at night. High nocturnal IOP coupled with low nocturnal systemic BP results in low ocular perfusion pressure and potential for unobserved damage to retinal tissues and the optic nerve. Circadian-related melatonin and sleep disorders also result in changes in IOP and ocular perfusion pressure that lead to the progression of glaucoma. In addition, impaired perception of light input due to glaucoma can subsequently lead to abnormal serum levels of melatonin, resulting in circadian rhythm misalignment. This disruption of the circadian rhythm also contributes to sleep and mood disorders, common in individuals with glaucoma. As regards treatment, glaucoma medications that lower nocturnal IOP without influencing nocturnal BP or diminishing circadian variation seem most effective. Conclusions Glaucoma progression is influenced by multiple physiological factors regulated by the circadian rhythm. Progression of the disease may also cause physiological changes that lead to circadian-related issues. Further research is warranted on the diurnal cycle, melatonin-mediated processes, and their influence on glaucoma management.

The role of hypertension in retinal blood flow alterations in open-angle glaucoma patients.

Abstract: Editor, W e would like to thank Grzybowski & Brona (2016) for their interest in our work regarding the use of chlorhexidine gluconate as an alternative to povidone–iodine for asepsis in intravitreal injections (IVI). Highlighting possible resistance to our antiseptic preparations is an important consideration for such prevalent procedures as intravitreal injections. While multiple outbreaks in other settings have been linked to contaminated chlorhexidine, typically these have been traced to use of contaminated water to prepare diluted preparations, failure to adequately disinfect bottles being reused to dispense chlorhexidine or inappropriate disinfection applications (rather than antisepsis applications) (Weber et al. 2007). For the outbreak referenced (vigeant), nonsterile water was used for dilution to 2% concentration anddistribution occurred in reusable non-sterile containers. We agree that more research is required to quantify theantimicrobial effectofaqueous chlorhexidine gluconate 0.1%, including demonstrated reduction in flora counts using chlorhexidine gluconate solutions,particularly inresistant bacterial strains. In our cohort, though, the rate of endophthalmitis was comparable with published rates suggesting efficacy in the clinical setting (Oakley & Vote 2016). However, multiple outbreaks have also been reported duetocontaminatediodophorsandhave typically represented intrinsic (manufacturing) contamination (Weber et al. 2007). Our understanding of iodophor chemistry improved from analysis of these outbreaks, highlighting that ‘free’ iodine (I2) contributes to thebactericidal activity with more dilute solutions demonstrating more rapid bactericidal action, possibly byweakening the iodine linkage to the carrier polymer povidone, with an accompanying increase in free iodine in solution (Berkelman et al. 1982;Weber et al. 2007). We agree with the authors’ points raised regarding the proven efficacy of povidone–iodine solutions and that reduced concentrations of povidone iodine, such as 2.5% used by Shimada et al. (2013), may be another method for reducing pain related to IVI while retaining efficacious antisepsis; however, patient comfort and pain studies are lacking in this area (Berkelman et al. 1982).We agree that future studies are warranted to find the optimal povidone–iodine concentration, balancing patient comfort with effective antisepsis. With the prevalence of intravitreal injections, these are studies that should be proceeding as the significance to patients of post-injection pain is not representative in our literature. Finally,we thank the authors for their valuable comments and highlight that our study was not intended to suggest chlorhexidine gluconate as a replacement antiseptic agent of choice. Rather, it was intended to highlight that postinjection pain from povidone–iodine sensitivity is significant for many patients. In our experience, this can be reduced for thosepatientswith the useof aqueous chlorhexidine gluconate 0.1%, with our study also providing clinical evidence for its utilization as antisepsis in the intravitreal injection setting.

Physical exercise and glaucoma: a review on the roles of physical exercise on intraocular pressure control, ocular blood flow regulation, neuroprotection and glaucoma-related mental health.

Abstract: The benefits of physical exercise on health and well-being have been studied in a wide range of systemic and ocular diseases, including glaucoma, a progressive optic neuropathy characterized by accelerated apoptosis of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and insufficient ocular perfusion have been postulated to be the two main theories in glaucoma development and progression. The effects of exercise in these two aspects have been demonstrated by numerous researches. A review in 2009 focusing on these two theories concluded that exercise results in transient IOP reduction but an inconsistent elevation in ocular perfusion. However, the majority of the studies had been conducted in healthy subjects. Over the past decade, technological advancement has brought forth new and more detailed evidence regarding the effects of exercise. Moreover, the neuroprotective effect of exercise by upregulation of neurotrophin and enhancement of mitochondrial function has been a focus of interest. Apart from visual impairment, the mental health issues in patients with glaucoma, which include anxiety and depression, should also be addressed. In this review, we mainly focus on publications from the recent years, so as to provide a comprehensive review on the impact of physical exercise on IOP, ocular perfusion, neuroprotection and mental health in patients with glaucoma.

Evaluating Effects of Switching Anti-Vascular Endothelial Growth Factor Drugs for Age-Related Macular Degeneration and Diabetic Macular Edema.

Abstract: Importance When a patient with neovascular age-related macular degeneration or diabetic macular edema does not respond to an initial anti–vascular endothelial growth factor agent, usually after several injections, ophthalmologists may switch to another anti–vascular endothelial growth factor agent. Authors of case series have suggested beneficial effects from switching. However, to our knowledge, there are no studies with an appropriate control group to evaluate how such patients would do without switching agents. Objective To assess outcomes in patients who have a poor initial response but continue treatment without switching agents. Design, Setting, and Participants We obtained data from 2 multicenter clinical trials, the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and the Diabetic Retinopathy Clinical Research Network (DRCR.net). Based on typical clinical reasons for switching agents, we developed “switching rules” at both 3 and 6 months after initiation of treatment. Using these switching rules, we identified a 3-month and a 6-month cohort of “treatment failures” from both CATT and DRCR.net studies. Interventions Although the cohorts from each study met criteria for switching, they were treated with the initial agent throughout the study (bevacizumab or ranibizumab in CATT and ranibizumab in DRCR.net). Main Outcomes and Measures Primary outcomes were change in visual acuity and change in central retinal thickness on optical coherence tomography from the 3- or 6-month visit at which switching rules were met. Results The 126 patients from CATT and the 59 patients from DRCR.net who were selected for the switching analysis were similar in age, sex and race/ethnicity to the overall study populations. Among the participants who met the criteria for switching, the CATT participants were a mean (SD) of 79.7 (7.8) years of age, 65.9% women, and 97.6% white, while the DRCR.net participants were a mean (SD) of 65.5 (9.3) years of age, 44.1% women, and 76.3% white In all 4 cohorts, there was a 3- to 5-letter improvement in mean visual acuity over the 3 months after the switching rules were met, although all patients continued on their originally assigned treatment. Mean central retinal thickness also improved by 40 to 70 μM. Conclusions and Relevance These results demonstrate the importance of having a comparison group to evaluate the effect of switching anti–vascular endothelial growth factor agents for treatment of neovascular age-related macular degeneration or diabetic macular edema. Without a comparison group, it is impossible to know whether any improvement observed after switching was related to the new treatment or was related to regression to the mean and time effects as observed in the 4 cohorts presented here. Randomization to switching or not switching drugs would provide a basis for valid conclusions about the effects of switching.

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy.

Abstract: Introduction: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments.Areas covered: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME. A literature search was performed using the following terms: anti-VEGF, DME, aflibercept, bevacizumab, ranibizumab, refractory macular edema, and VEGF.Expert opinion: Focal extrafoveal DME may be treated first-line with laser. In patients with center-involving DME and only mild vision loss, consider starting treatment with bevacizumab, especially when cost is an issue, whereas aflibercept may be considered more strongly in patients with moderate visual loss or worse. There are no standard protocols that define ‘treatment failure,...