Injectable Devices for Delivery of Liquid or Solid Protein Formulations.

Sustained delivery of protein therapeutics remains a largely unsolved problem across anatomic locations. Miniaturized devices that can provide sustained delivery of protein formulations have the potential to address this challenge via minimally invasive administration. In particular, methodologies that can optimize protein formulation independent of device manufacture have the greatest potential to provide a platform suitable for wide applications. The techniques developed here demonstrate the fabrication of tubular devices for sustained release of protein therapeutics. Utilizing a dip-casting process, fine-scale tubes can be reliably produced with wall thickness down to 30 µm. Techniques were developed that enabled effective loading of either solid or liquid formulations, while maintaining a cylindrical form-factor compatible with placement in a 22-gauge needle. Further, highly compacted protein pellets that approach the expected density of the raw materials were produced with a diameter (∼300 µm) suitable for miniaturized devices. Release from a solid-loaded device was capable of sustaining release of a model protein in excess of 400 days. Given significant interest in ocular applications, intravitreal injection was demonstrated in a rabbit model with these devices. In addition, to simulate repeated injections in ocular applications, serial intravitreal injection of two devices in a rabbit model demonstrated acceptable ocular safety without significant intraocular inflammation from clinical exam and histology.

Macular Atrophy Incidence, Progression, and Visual Acuity Effects in 5-Year Treatment of Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Macular atrophy (MA) contributes to declining vision during prolonged anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) so greater understanding of its incidence, evolution, and impact on visual acuity is merited. MATERIALS AND METHODS: This is a retrospective review of nAMD patients receiving anti-VEGF therapy for ≥ 5 years. Near-infrared reflectance images and vision data were extracted every 6 months. MA lesion areas were measured using ImageJ. RESULTS: Vision showed a mean decline of -1.2 letters/year. Eyes with MA showed a greater decrease of -1.6 letters/year compared to eyes without MA (-0.7 letters/year). Cumulative incidence of MA was 38% at 5 years. MA was significantly associated with declining vision, showing a -0.7 letter decrease for every 1 mm2 increase in lesion size. CONCLUSION: Over a 5-year course of nAMD treatment, MA affected most eyes, and MA progression was significantly associated with vision decline. [Ophthalmic Surg Lasers Imaging Retina 2022;53:546-552.].

Retinal and choroidal manifestations of COVID-19.

PURPOSE OF REVIEW: The novel coronavirus disease in 2019 (COVID-19) has a wide range of systemic manifestations. Ocular manifestations are now well recognized, with conjunctivitis being the most common. Posterior segment involvement is uncommon and has mainly been described in case reports. This review provides an overview of the posterior segment involvement of COVID-19. RECENT FINDINGS: Severe acute respiratory syndrome coronavirus 2 affects the retina and the choroid through either direct entry or triggering an indirect inflammatory response. Majority of the retinal findings is a result of microvascular derangement leading to cotton wool spots, intraretinal hemorrhages, paracentral acute middle maculopathy, acute macular neuroretinopathy, or retinal vein occlusions. Rarely, inflammation involving the retina or the choroid, or reactivation of previously quiescent uveitis, can be seen. SUMMARY: It is important to recognize the possible correlation between ophthalmic conditions and COVID-19 as it can aid in diagnosis, management, and mitigation of the disease.

Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: A claims-based analysis.

BACKGROUND: Ocular inflammation causes significant visual morbidity in the United States, yet little is known about the epidemiology of infectious uveitis and scleritis. This study aims to evaluate the epidemiology of infectious uveitis/scleritis employing a large national medical claims database. METHODS: This was a retrospective, case-control study, employing Optum's de-identified Clinformatics® Data Mart Database, containing data from 21.5 million privately insured individuals with enrollment for at least 15 months within 2007-2015. Inclusion in the uveitis/scleritis sample required an index uveitis/scleritis diagnosis based on International Classification of Diseases, Ninth Revision (ICD-9) codes. Exclusion criteria included index date within 3 months after intraocular surgery. Rates for uveitis/scleritis were determined by anatomic site. Multivariable logistic regression analyses were performed to determine odds ratios for the incidence and prevalence of uveitis/scleritis by anatomic category. FINDINGS: Infectious etiologies accounted for less than 20% of uveitis/scleritis, with mean rates of 18.9 (incidence) and 60.6 (prevalence) per 100,000 persons. The mean prevalences of infectious anterior, intermediate, posterior, panuveitis, and scleritis were 27.7, 0.17, 23.4, 4.4, and 4.6, per 100,000, respectively. Overall risk of prevalent infectious uveitis/scleritis increased with age (OR>3.3 for each decade over age 18, p<0.01), female sex (OR = 1.2, p<0.01), non-Hispanic white race (OR<1 for all other races, p<0.01), as well as the East South Central census division (OR = 1.2, p<0.01), comprising Alabama, Kentucky, Missouri, and Tennessee. Medical comorbidities, including HIV infection (OR = 6.4, p<0.01) and rheumatologic disease (OR = 1.9, p<0.01), were common in the infectious uveitis/scleritis cohort. CONCLUSIONS: The incidence and prevalence of infectious uveitis/scleritis in the United States were higher than previously reported estimates but remained lower than in developing countries. Rates varied by age, sex, race, and medical comorbidities, and may reflect differential susceptibility to various infectious agents with disparate geographic distributions within the United States.

Bilateral Choroidal Neovascularization and Chorioretinal Anastomosis in Autosomal Recessive Bestrophinopathy.

Purpose: This case report discusses a case of bilateral chorioretinal anastomoses in autosomal recessive bestrophinopathy (ARB) unresponsive to antivascular endothelial growth factor therapy and its associated optical coherence tomography angiography (OCTA) findings. Methods: An observational case report is presented. Results: An 8-year-old girl initially presented at age 2 years with multifocal midperipheral yellow subretinal deposits with intraretinal and subretinal fluid. She was treated with intravitreal injections of bevacizumab in both eyes with minimal response. OCTA revealed the presence of choroidal neovascularization and chorioretinal anastomoses. Molecular diagnosis of ARB was achieved with the identification of compound heterozygous mutations in BEST1, including a silent exonic splicing mutation. Conclusions: Subretinal or intraretinal fluid in ARB may be exacerbated by the presence of chorioretinal anastomosis detected on OCTA. Silent exonic mutations that cause no amino acid change can be overlooked but are pathogenic in ARB.

Anticoagulation Patterns in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention in an Academic Center.

A common dilemma facing physicians treating patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) is the management of oral anticoagulation (OAC) therapy, because there is also an indication for dual antiplatelet therapy in these patients. The purpose of this study was therefore to evaluate anticoagulation patterns in this patient population in an attempt to identify patterns of risk factors that may influence OAC prescribing habits. This retrospective study entailed a review of a total of 4,648 patients from two academic hospitals who underwent PCI between 2008 and 2016. We ultimately included 211 patients who had AF and an indication for OAC. Chart review revealed patients' risk factors, CHA2DS2-VASc and HAS-BLED scores, and antithrombotic regimens. Only 105 (49.8%) patients who met the indications for OAC were actually placed on OAC post-PCI. There was no significant relationship between discharge on OAC and HAS-BLED score (t = 0.14; p = 0.44) or CHA2DS2-VASc score (t = 0.76; p = 0.22). Patients younger than 65 years of age were prescribed more triple therapy (56% versus 33%; p < 0.01) or any OAC (69% versus 41%; p < 0.01) on discharge in comparison with patients 65 years of age or older. The older patient group had a significantly higher average CHA2DS2-VASc score (4.4 versus 3.2; p < 0.01) and a higher average HAS-BLED score (2.8 versus 2.4; p < 0.01). Ultimately, this study indicated that less than half of AF patients with an indication for OAC were placed on OAC post-PCI. There was no association between discharge on OAC and CHA2DS2-VASc score, HAS-BLED score, or any other individual risk factor, with the exception of age.

Assessment of Urologists' Knowledge of Intraoperative Floppy Iris Syndrome.

OBJECTIVES: To assess urologists' awareness of intraoperative floppy iris syndrome. MATERIALS AND METHODS: A questionnaire composed of 21 questions was emailed to all of the Urology residency programs in the U.S. and all members of the Western section of the American Urological Association. Responses were collected and analyzed using statistical software. RESULTS: A total of 175 responses were collected from residents, fellows, and attending physicians from a wide range of geographic locations, subspecialties, and practice settings. Thirty percent of the urologists would routinely discuss intraoperative floppy iris syndrome with patients prior to start of benign prostate hyperplasia treatment. Twenty-one percent of the respondents never asked patients about ophthalmologic conditions prior to benign prostate hyperplasia treatment. If patients had concurrent visual complaints, only 37% of the respondents would routinely encourage patients to speak to an ophthalmologist and only 13% would routinely refer patients to an ophthalmologist. A comparison among the subgroups based on training status and practice settings further showed that a significantly higher percentage of residents would not ask about visual complaints or refer patients with visual complaints to an ophthalmologist compared with fellows and attending physicians (P <.01); however, there was no significant difference between urologists in academic and nonacademic settings (P >.05). CONCLUSION: Despite continuing effort to educate physicians about intraoperative floppy iris syndrome, there still exists a knowledge gap that may compromise patient care and further education is needed.

Impaired Retinal Perfusion Resulting From Vitreoretinal Traction: A Mechanism of Retinal Vascular Insufficiency.

BACKGROUND AND OBJECTIVE: To demonstrate vitreoretinal traction as a mechanism of abnormal retinal vascular perfusion. PATIENTS AND METHODS: Retrospective report of three cases demonstrating vitreoretinal traction concurrent with abnormal retinal perfusion. Subjects were retrospectively identified based on clinical records from two tertiary care retina subspecialty practices. All subjects underwent complete ophthalmic examination and ancillary testing as necessary for their standard clinical care. Vascular perfusion was assessed by one or more methods, including wide-field fluorescein angiography and optical coherence tomography angiography (OCTA). Vitreoretinal traction was assessed by clinical examination; intraoperative surgical observations; and fundus imaging, including wide-field, red-free, and color images as well as OCT. RESULTS: Three cases are shown in which vitreoretinal traction was clearly documented and correlated with abnormal retinal vascular perfusion. Abnormal vascular perfusion correlated with the distribution of vessels affected by vitreoretinal traction in all cases. Vascular perfusion normalized in all cases after surgery was used to relieve vitreoretinal traction. CONCLUSION: The authors demonstrate that vitreoretinal traction can alter retinal vascular perfusion in a reversible fashion. These results suggest that there can be a direct mechanical effect of vitreous traction on retinal vascular perfusion. Further advances in wide-field imaging, wide-field OCT, and OCTA will help better evaluate this cause of retinal vascular insufficiency.