SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Teleophthalmology Using Remote Retinal Imaging During the COVID-19 Pandemic.

Introduction: Lower insurance reimbursements have limited the financial sustainability of remote eye screening programs. Greater utilization and insurance coverage for teleophthalmology screening during the coronavirus disease 2019 (COVID-19) pandemic in 2020 may enhance awareness and expand remote retinal imaging services. This retrospective cross-sectional study evaluates utilization and insurance coverage for remote retinal imaging in the United States in 2020. Methods: We analyzed teleretinal imaging utilization and insurance payments from January 1 to December 31, 2020, using the Optum Labs Data Warehouse, a comprehensive national database of deidentified administrative claims for commercial and Medicare Advantage enrollees in the United States. We evaluated frequency of claims and insurance payment for services using the Current Procedural Terminology codes 92227 and 92228 for remote eye imaging by any provider, and 92250 for fundus photography by non-eye care providers. Results: The use of remote retinal imaging in the United States declined rapidly during the initial COVID-19 lockdown from 3,627 claims in February 2020 to 1,414 claims in April 2020, but returned to 3,133 claims by December 2020, similar to mean prepandemic levels in 2019 (2,841 ± 174.8 claims). The proportion of insurance payments for remote imaging increased temporarily from 47.4% in February to 56.7% in April, and then returned to 45.9% in December of 2020. Discussion: Utilization of remote retinal imaging declined steeply, while the insurance coverage increased during the initial COVID-19 lockdown in 2020, but returned to prepandemic levels by end of the year. Changes in utilization and relaxed restrictions on insurance reimbursements for teleophthalmology during the COVID-19 pandemic were not sustained.

Barriers to Implementation of Teleretinal Diabetic Retinopathy Screening Programs Across the University of California.

Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (<5% to 15%) and average image interpretation time (1-5 days). Patient education, resource availability, and infrastructural support were identified as barriers to DR teleretinal screening. Cost and integration into existing technology infrastructures were identified as barriers to AI integration in DR screening. Conclusions: Despite the potential to increase access to care, there remain several barriers to widespread implementation of DR teleretinal screening. More research is needed to develop best practices to overcome these barriers.

Clinical presentation, treatment, and genetic and histopathological analysis of juvenile cataracts and secondary glaucoma in a rhesus macaque (Macaca mulatta).

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

IDIOPATHIC MULTIFOCAL CHOROIDITIS WITH SERPIGINOUS-LIKE PERIPAPILLARY CHORIORETINAL ATROPHY.

PURPOSE: To report nine cases of multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. METHODS: A retrospective observational case series of eyes with multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. Multimodal imaging findings were reviewed and presented. RESULTS: Fifteen eyes of 9 patients (6 women and 3 men), with a mean age of 48.1 years (median, 46 years; range, 23-74 years), presented with multifocal choroiditis serpiginous-like peripapillary chorioretinal atrophy. All 15 eyes presented with serpiginoid peripapillary changes and had discrete patches of atrophy or punched-out scars in the posterior pole or periphery. Eleven eyes (73.3%) had cone-shaped retinal pigment epithelium elevations on optical coherence tomography, 10 eyes (66.7%) had mild vitritis, and 4 eyes (26.7%) had peripheral curvilinear streak lesions. Three eyes (20%) had choroidal neovascularization. All patients responded well to treatment with systemic immunosuppression, local corticosteroid injections, and/or intravitreal anti-vascular endothelial growth factor injections. CONCLUSION: Multifocal choroiditis may present with peripapillary chorioretinal changes resembling a serpiginous-like choroiditis in addition to the classic findings of patches of atrophy or punched-out scars in the posterior pole or periphery, cone-shaped retinal pigment epithelium elevated on optical coherence tomography and peripheral curvilinear streak lesions.

Age-related changes in the rhesus macaque eye.

PURPOSE: To assess age-related changes in the rhesus macaque eye and evaluate them to corresponding human age-related eye disease. METHODS: Data from eye exams and imaging tests including intraocular pressure (IOP), lens thickness, axial length, and retinal optical coherence tomography (OCT) images were evaluated from 142 individuals and statistically analyzed for age-related changes. Quantitative autofluorescence (qAF) was measured as was the presence of macular lesions as related to age. RESULTS: Ages of the 142 rhesus macaques ranged from 0.7 to 29 years (mean = 16.4 years, stdev = 7.5 years). Anterior segment measurements such as IOP, lens thickness, and axial length were acquired. Advanced retinal imaging in the form of optical coherence tomography and qAF were obtained. Quantitative assessments were made and variations by age groups were analyzed to compare with established age-related changes in human eyes. Quantitative analysis of data revealed age-related increase in intraocular pressure (0.165 mm Hg per increase in year of age), ocular biometry (lens thickness 7.2 µm per increase in year of age; and axial length 52.8 µm per increase in year of age), and presence of macular lesions. Age-related changes in thicknesses of retinal layers on OCT were observed and quantified, showing decreased thickness of the retinal ganglion cell layer and inner nuclear layer, and increased thickness of photoreceptor outer segment and choroidal layers. Age was correlated with increased qAF by 1.021 autofluorescence units per increase in year of age. CONCLUSIONS: The rhesus macaque has age-related ocular changes similar to humans. IOP increases with age while retinal ganglion cell layer thickness decreases. Macular lesions develop in some aged animals. Our findings support the concept that rhesus macaques may be useful for the study of important age-related diseases such as glaucoma, macular diseases, and cone disorders, and for development of therapies for these diseases.

NATURAL HISTORY AND PREDICTORS OF VISION LOSS IN EYES WITH DIABETIC MACULAR EDEMA AND GOOD INITIAL VISUAL ACUITY.

PURPOSE: To identify clinical and anatomic factor-associated vision loss in eyes with treatment-naïve diabetic macular edema and good initial visual acuity. METHODS: Retrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy. RESULTS: Fifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094). CONCLUSION: In eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

Visible light OCT improves imaging through a highly scattering retinal pigment epithelial wall.

Here we provide a counter-example to the conventional wisdom in biomedical optics that longer wavelengths aid deeper imaging in tissue. Specifically, we investigate visible light optical coherence tomography of Bruch's membrane (BM) in the non-pathologic eyes of humans and two mouse strains. Surprisingly, we find that shorter visible wavelengths improve the visualization of BM in pigmented eyes, where it is located behind a highly scattering layer of melanosomes in the retinal pigment epithelium (RPE). Monte Carlo simulations of radiative transport suggest that, while absorption and scattering are higher at shorter wavelengths, detected multiply scattered light from the RPE is preferentially attenuated relative to detected backscattered light from the BM.

Emerging Concepts in the Treatment of Diabetic Retinopathy.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults in the developed world. This review discusses the current approach to managing the disease, such as glycemic and blood pressure control, as well as laser photocoagulation, as well as emerging concepts and controversies on novel therapies. RECENT FINDINGS: In recent years, the rise of intraocular anti-angiogenesis treatments is changing the paradigm of classic laser photocoagulation in the management of DR, but its long-term benefits remain an area of controversy. We also discuss new targets including anti-inflammation, neuroprotection, and novel laser technologies. Finally, we discuss new advances in retinal imaging that has vastly improved the diagnosis and management of DR. Diagnosis and management of diabetic retinopathy is a rapidly progressing field. Emerging concepts in ophthalmic imaging, medical treatments, and surgical approaches provide insights into how DR management will evolve in the near future.

OUTCOMES OF PNEUMATIC RETINOPEXY PERFORMED BY VITREORETINAL FELLOWS.

PURPOSE: To evaluate the anatomical and visual outcomes of patients who underwent pneumatic retinopexy by vitreoretinal fellows. METHODS: We included 198 eyes (198 patients) that underwent pneumatic retinopexy by vitreoretinal fellows at a single academic institution between November 2002 and June 2016. Main outcomes were single-operation success and final anatomical success in retinal reattachment, as well as visual acuity at 3 months and 6 months after treatment. RESULTS: Single-operation success rate was 63.6% at 3 months and 59.5% at 6 months. Final anatomical reattachment was achieved in 92.9% (n = 184) and 96.6% (n = 143) at 3 months and 6 months, respectively. Logarithm of the minimum angle of resolution visual acuity improved from 0.72 ± 0.1 (∼20/100 Snellen) at baseline to 0.36 ± 0.06 (∼20/40 Snellen) at 6 months (P < 0.001). There was no statistical difference in anatomical success rates or visual outcomes between cases performed by first- or second-year fellows (P > 0.50). Single-operation success was associated only with size of detachment (P = 0.01). Visual outcome was associated with macula status at baseline (P = 0.032) and number of reoperations (P < 0.001). CONCLUSION: Anatomical and visual outcomes of fellow-performed pneumatic retinopexy are comparable with those reported in the previous literature.

Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD). Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA). Results: The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >±1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages. Conclusions: ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.

Comparison of chorioretinal layers in rhesus macaques using spectral-domain optical coherence tomography and high-resolution histological sections.

Nonhuman primates are important preclinical models of retinal diseases because they uniquely possess a macula similar to humans. Ocular imaging technologies such as spectral-domain optical coherence tomography (SD-OCT) allow noninvasive, in vivo measurements of chorioretinal layers with near-histological resolution. However, the boundaries are based on differences in reflectivity, and detailed correlations with histological tissue layers have not been explored in rhesus macaques, which are widely used for biomedical research. Here, we compare the macular anatomy and thickness measurements of chorioretinal layers in rhesus macaque eyes using SD-OCT and high-resolution histological sections. Images were obtained from methylmethacrylate-embedded histological sections of 6 healthy adult rhesus macaques, and compared with SD-OCT images from 6 age-matched animals. Thicknesses of chorioretinal layers were measured across the central 3 mm macular region using custom semi-automated or manual software segmentation, and compared between the two modalities. We found that histological sections provide better distinction between the ganglion cell layer (GCL) and inner plexiform layer (IPL) than SD-OCT imaging. The first hyperreflective band between the external limiting membrane (ELM) and retinal pigment epithelium (RPE) appears wider on SD-OCT than the junction between photoreceptor inner and outer segments seen on histology. SD-OCT poorly distinguishes Henle nerve fibers from the outer nuclear layer (ONL), while histology correctly identifies these fibers as part of the outer plexiform layer (OPL). Overall, the GCL, inner nuclear layer (INL), and OPL are significantly thicker on histology, especially at the fovea; while the ONL, choriocapillaris (CC), and outer choroid (OC) are thicker on SD-OCT. Our results show that both SD-OCT and high-resolution histological sections allow reliable measurements of chorioretinal layers in rhesus macaques, with distinct advantages for different sublayers. These findings demonstrate the effects of tissue processing on chorioretinal anatomy, and provide normative values for chorioretinal thickness measurements on SD-OCT for future studies of disease models in these nonhuman primates.

Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration.

PURPOSE: Appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral-domain optical coherence tomography (SD OCT). We aimed to build SD OCT-based risk assessment models for 5-year new onset of GA and central GA on CP. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Age-Related Eye Disease Study 2 Ancillary SD OCT study participants with age-related macular degeneration (AMD) with bilateral large drusen or noncentral GA and at least 1 eye without advanced disease (n = 317). METHODS: For 1 eye per participant, qualitative and quantitative SD OCT variables were derived from standardized grading and semiautomated segmentation, respectively, at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator. MAIN OUTCOME MEASURES: New onset of CP-visible GA and central GA. RESULTS: Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SD OCT factors (P < 0.001-0.03) were: hyperreflective foci and retinal pigment epithelium (RPE) layer atrophy or absence, followed by choroid thickness in absence of subretinal drusenoid deposits, photoreceptor outer segment loss, RPE drusen complex volume, and RPE drusen complex abnormal thinning volume. For central GA, the factors (P < 0.001) were RPE drusen complex abnormal thinning volume, intraretinal fluid or cystoid spaces, hyperreflective foci, and RPE layer atrophy or absence. The models yielded a calculator that computes the probabilities of CP-visible, new-onset GA and central GA after 1 to 5 years. CONCLUSIONS: For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model-based on age and SD OCT segmentation, drusen characteristics, and retinal pathology-for progression to CP-visible GA over up to 5 years. This calculator may simplify SD OCT grading and with future validation has a promising role as a clinical prognostic tool.

Surgical Drainage of Large Macular Cystoid Spaces in Coats Disease.

Purpose: To describe an option of surgically draining large macular cystoid spaces in a patient with Coats disease. Methods: A case and its findings were analyzed. Results: A standard pars plana vitrectomy was performed to aspirate large macular cystoid spaces using a subretinal cannula with intraoperative optical coherence tomography guidance. Because of the viscous nature of the chronic fluid and lipid exudates, the contents of the large cystoid spaces were drained through a retinotomy using a soft-tipped aspiration cannula. Postoperative follow-up after surgical drainage showed immediate resolution of the macular cystoid spaces and gradual resolution of the dense subfoveal exudates over 1 year. Although surgical intervention led to the eventual resolution of the macular edema and exudates, visual recovery was limited by the chronicity of the condition. Conclusions: Surgical drainage of large macular cystoid spaces in Coats disease can be achieved in eyes that are refractory to medical management. Earlier surgical intervention in select cases may allow for visual rehabilitation.

Factors Involved in Anti-VEGF Treatment Decisions for Neovascular Age-Related Macular Degeneration: Insights from Real-World Clinical Practice.

Background: Anti-vascular endothelial growth factor (anti-VEGF) agents are widely prescribed for the treatment of neovascular age-related macular degeneration (nAMD). Although studies have investigated patient choice of anti-VEGF agent, little is known regarding factors that influence physician preference of anti-VEGF agent for their patients. Objective: To describe physician rationale and challenges in prescribing anti-VEGF treatments for patients with nAMD. Methods: Data were drawn from the Adelphi Real World nAMD Disease Specific Programme™, a cross-sectional survey with retrospective data capture of physicians and their patients with nAMD in the United States between October 2021 and May 2022. Physicians (n = 56) reported data for up to 13 consecutively consulting patients (n = 451), including current anti-VEGF treatments used, factors affecting physicians' choice of anti-VEGF agent and treatment strategy, and restrictions on specific agents. Results: Most physicians prefer employing a "treat-and-extend" treatment strategy, over "fixed interval" or "pro re nata" strategies. However, in routine clinical practice, "treat-and-extend" was reported for less than half of nAMD-diagnosed eyes. Top factors influencing physician choice of anti-VEGF agent and treatment strategy included maximizing clinical benefit (eg visual acuity gains and fluid control), patient convenience, and reducing out-of-pocket costs. However, physicians also reported facing substantial roadblocks in prescribing their choice of anti-VEGF agent, including restrictions on approved agents and gaps in insurance coverage. Persistent fluid was the most common physician-selected reason for switching a patient away from an anti-VEGF agent. Conclusion: Physicians face barriers to prescribing their preferred anti-VEGF agents in real-world healthcare settings. Overcoming these challenges may improve treatment outcomes for patients with nAMD.

People with wet age-related macular degeneration (wet AMD) have problems with their eyesight that can lead to blindness if left untreated. Eye doctors (ophthalmologists) use a class of medicine called anti-VEGF agents to treat people with wet AMD. However, eye doctors often face challenges in prescribing their anti-VEGF agent of choice. We surveyed eye doctors to determine the reasons why they preferred some anti-VEGF agents over others, as well as the barriers to prescribing these anti-VEGF agents. Eye doctors reported that they usually choose a specific anti-VEGF agent because it leads to better vision, has lower cost for people with wet AMD, or may reduce the number of appointments needed for people with wet AMD. Eye doctors also noted that they face challenges in treating people with wet AMD, including restrictions and limited insurance coverage for certain anti-VEGF agents. Solving these problems could help eye doctors use their medicine of choice and improve eyesight even more when they treat people with wet AMD.

Teleophthalmology provides earlier eye care access for patients with newly-diagnosed diabetes.

Purpose: Timely diagnosis of diabetic retinopathy is important in preventing vision loss. This study aims to determine if remote retinal imaging enables earlier eye care access among newly-diagnosed diabetic patients. Design: Retrospective cohort study. Methods: Using the OptumLabs® Data Warehouse - a longitudinal, real-world dataset containing deidentified administrative claims and electronic health record (EHR) data, we included 968 846 adults with newly diagnosed type 2 diabetes and at least 1 year of continuous enrollment. We compared time from initial diabetes diagnosis to first eye exam by remote screening or in-person eye exam. Results: We found that at year 1 after diagnosis, 5459 (0.56%) patients underwent remote imaging and 208 023 (21.5%) underwent in-person exam. The mean (95% CI) time to eye exam was 3.48 (3.38-3.58) months for remote imaging and 4.22 (4.20-4.23) months for in-person visits (p < 0.0001). Interestingly, 27.5% of remote screenings were performed on the same day of diabetes diagnosis. Excluding same-day encounters, mean time to eye exam was 4.80 (4.68-4.91) months for remote imaging and 4.85 (4.83-4.86) months for in-person eyecare (p = 0.4). Conclusions: Thus, teleophthalmology may enable earlier eye care access among patients with newly-diagnosed diabetes, primarily with same-day screenings. Increased adoption of teleretinal screening may enable earlier detection of diabetic retinopathy and prevent vision loss.