Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications.

PURPOSE: Evaluate the risk of diabetic retinopathy progression and systemic vascular events, including death, in patients with non-proliferative diabetic retinopathy (NPDR) with obstructive sleep apnea (OSA). DESIGN: Retrospective cohort study. METHODS: Electronic chart query using TriNetX (Cambridge, MA, USA), an electronic health records network comprising data from over 124 million patients. Patients with NPDR with and without OSA were identified. Patients were excluded if they had history of proliferative disease (PDR), diabetic macular edema (DME), or prior ocular intervention (intravitreal injection, laser, or pars plana vitrectomy). Propensity score matching was performed to control for baseline demographics and comorbidities. Rate of progressing to vision threatening complications (VTCs), need for ocular intervention, and systemic events was measured at 1, 3, and 5 years. RESULTS: 11,931 patients in each group were analyzed after propensity score matching. There was elevated risk of PDR in the OSA cohort at 1 (RR: 1.34, P<0.001), 3 (RR: 1.31, P<0.001), and 5 years (RR: 1.28, P<0.001). There was elevated risk of DME in the OSA group at all time points: 1 (RR: 1.31, P<0.001), 3 (RR: 1.19, P<0.001), and 5 years (RR: 1.18, P<0.001). With respect to ocular interventions, there was an increased risk of intravitreal injection in OSA patients at 1 (RR: 1.59, P<0.001), 3 (RR: 1.58, P<0.001), and 5 years (RR: 1.54, P<0.001), and similar trends were noted with laser photocoagulation, but not vitrectomy. Regarding systemic events, NPDR patients with OSA had a greater risk of stroke (1 year RR: 1.80, P<0.001; 3 year RR: 1.56, P<0.001; 5 year RR: 1.49, P<0.001), myocardial infarction (1 year RR: 1.51, P<0.001; 3 year RR: 1.46, P<0.001; 5 year RR: 1.43, P<0.001), and death (1 year RR: 1.31, P<0.001; 3 year RR: 1.19, P<0.001; 5 year RR: 1.15, P<0.001). CONCLUSIONS: There is an increased rate of DR progression to VTCs, need for ocular intervention, and systemic complications, including death, for patients with OSA. We emphasize the need for improved screening measures of patients with NPDR and potential OSA.

Widefield Swept-Source OCTA Findings in HELLP Syndrome: Choroidal Infarcts.

PURPOSE: Pre-eclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome have been previously implicated with ophthalmic complications including serous retinal detachments and disorders of the choroidal vasculature. Herein, we report a case of macular serous detachment associated with HELLP syndrome in which wide field swept-source optical coherence tomography angiography (WF SS-OCTA) was used. METHODS: Retrospective case report of a patient who developed HELLP syndrome. The patient underwent multimodal retinal imaging and wide field swept-source OCT angiography (WF SS-OCTA) (PLEX® Elite 9000, Carl Zeiss Meditec Inc.). RESULTS: A 36-year-old female patient diagnosed with HELLP syndrome presented with bilateral blurry vision. At presentation, dilated fundus exam revealed localized subretinal fluid in the macula. WF SS-OCTA showed areas of peripapillary and subfoveal flow signal attenuation in the choroid OD, consistent with choroidal infarction. CONCLUSIONS: These findings support the hypothesis that HELLP syndrome is associated with vascular changes that lead to choroidal dysfunction and subsequent serous retinal detachments. Furthermore, this case highlights a role for the non-invasive WF SS-OCTA technology in diagnosing and further characterizing the pathophysiology without the use of dye-based angiography.

Initial Therapy of Panretinal Photocoagulation vs Anti-VEGF Injection for Proliferative Diabetic Retinopathy.

Importance: While combined treatment of anti-vascular endothelial growth factor (VEGF) injections plus panretinal photocoagulation (PRP) is a common approach for treating proliferative diabetic retinopathy (PDR) in the clinical practice setting, large randomized clinical trials typically use monotherapy. Subsequently, information is limited as to whether the order of treatment when combining PRP and anti-VEGF injections for PDR affects outcomes. Objective: To compare outcomes of patients with PDR treated with PRP and subsequent anti-VEGF injections with outcomes of matched patients treated with anti-VEGF injections and subsequent PRP. Design, Setting, and Participants: This retrospective cohort study used data from January 2003 to January 2024 in the TriNetX aggregated electronic health records network, with data analysis performed in January 2024. Patients with PDR treated with PRP and anti-VEGF injections were eligible for inclusion. Exposures: Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP. Main Outcomes and Measures: The primary outcome was the need for pars plana vitrectomy (PPV), defined by Current Procedural Terminology codes 67040 or 67113. The secondary outcome included incidence of PPV, vitreous hemorrhage (VH), or tractional retinal detachment (TRD). Relative risk ratios, relative risk differences, and 95% CIs were all calculated for univariate comparison of the cohorts and the development of primary outcomes after matching. Results: Before propensity score matching (PSM), which controlled for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR treated with PRP first and subsequent anti-VEGF injections and 1549 patients with PDR treated with anti-VEGF injections and subsequent PRP were included. Post-PSM, mean (SD) participant age was 63.0 (13.1) years in cohort 1 (PRP and subsequent anti-VEGF injection) and 63.0 (12.4) years in cohort 2 (anti-VEGF injection and subsequent PRP). Of 1377 total participants in each cohort, 641 patients (46.6%) and 663 patients (48.1%) in cohorts 1 and 2 were female, respectively. Treatment with PRP first and subsequent anti-VEGF injection was associated with higher rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55-2.27; risk difference [RD], 8.93%; 95% CI, 6.31%-11.55%; P < .001), with similar associations at 6 months, 1 year, and 3 years. Treatment with PRP and subsequent anti-VEGF injection was associated with higher rates of VH at 5 years (RR, 1.40; 95% CI, 1.09-1.80; RD, 6.47%; 95% CI, 1.66%-11.29%; P < .001) and TRD at 5 years (RR, 1.85; 95% CI, 1.35-2.53; RD, 4.31%; 95% CI, 2.10%-6.52%; P < .001), with similar findings at 6 months, 1 year, and 3 years compared with patients treated with anti-VEGF injection and subsequent PRP. Conclusions and Relevance: In this retrospective cohort study, findings suggest that patients with PDR treated with PRP first then subsequent anti-VEGF injection are more likely to undergo PPV for VH and TRD compared with matched patients treated with anti-VEGF agents first, then PRP. These findings support the need for further investigations to determine if the order of PRP and anti-VEGF injections should be considered when treating patients with PDR.

Progression to Pars Plana Vitrectomy in Patients With Proliferative Diabetic Retinopathy.

Importance: The Diabetic Retinopathy Clinical Research Network Protocol S suggested that vitrectomy for vitreous hemorrhage (VH) or tractional retinal detachment (TRD) was more common among eyes assigned initially to panretinal photocoagulation (PRP) vs anti-vascular endothelial growth factor (anti-VEGF) for proliferative diabetic retinopathy (PDR). These clinical implications warrant further evaluation in the clinical practice setting. Objective: To explore outcomes of PDR treated with PRP monotherapy compared with matched patients treated with anti-VEGF monotherapy. Design, Setting, and Participants: Retrospective cohort study using an aggregated electronic health records research network. Patients with PDR who received PRP or anti-VEGF monotherapy between January and September 2023 were included before propensity score matching. Patients were excluded with 6 or fewer months' follow-up after monotherapy or with a combination of PRP and anti-VEGF. Data were analyzed in September 2023. Exposures: Patients with new PDR diagnoses stratified by monotherapy with PRP or anti-VEGF agents using Current Procedural Terminology code. Main Outcome Measures: Incidence of pars plana vitrectomy (PPV), VH, or TRD. Results: Among 6020 patients (PRP cohort: mean [SD] age, 64.8 [13.4]; 6424 [50.88%] female; 3562 [28.21%] Black, 6180 [48.95%] White, and 2716 [21.51%] unknown race; anti-VEGF cohort: mean [SD] age, 66.1 [13.2]; 5399 [50.52%] male; 2859 [26.75%] Black, 5377 [50.31%] White, and 2382 [22.29%] unknown race) who received treatment, PRP monotherapy was associated with higher rates of PPV when compared with patients treated with anti-VEGF monotherapy at 5 years (RR, 1.18; 95% CI, 1.05-1.36; RD, 1.37%; 95% CI, 0.39%-2.37%; P < .001), with similar associations at 1 and 3 years. PRP monotherapy was associated with higher rates of VH at 5 years (relative risk [RR], 1.72; 95% CI, 1.52-1.95; risk difference [RD], 7.05; 95% CI, 5.41%-8.69%; P < .001) and higher rates of TRD at 5 years (RR, 2.76; 95% CI, 2.26-3.37; RD, 4.25%; 95% CI, 3.45%-5.05%; P < .001), with similar magnitudes of associations at 6 months, 1 year, and 3 years, when compared with patients treated with anti-VEGF monotherapy. Conclusions and Relevance: These findings support the hypothesis that patients with PDR treated with PRP monotherapy are more likely to develop VH, TRD, and undergo PPV when compared with matched patients treated with anti-VEGF monotherapy. However, given the wide range in relative risk, confounding factors may account for some of the association between PRP vs anti-VEGF monotherapy and outcomes evaluated.

Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study.

PURPOSE: To examine the effects of glucagon-like peptide-1 receptor (GLP-1) agonists compared to SGLT-2 inhibitors on diabetic retinopathy. DESIGN: Retrospective clinical cohort study using TriNetX, a federated electronic health records network comprising multiple healthcare organizations. METHODS: Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of nonproliferative diabetic retinopathy (PDR) and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with a history of PDR prior to initiation of treatment were excluded. The rate of progression to PDR and rate of development of diabetic macular edema (DME) were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of PDR. Main outcomes included rate and relative risk (RR) of progression to PDR and risk of DME in the GLP-1 agonist group versus the SGLT-2 inhibitor group. RESULTS: A total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 and 3 years after initiation of therapy, a higher rate of progression of PDR was noted (RR: 1.26, CI 1.04-1.51, P = .017 at 1 year, RR: 1.284, CI 1.1-1.499, P = .002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of DME noted at 3 months (RR: 1.192, CI 1.059-1.276, P = .002), 6 months (RR: 1.22, CI 1.13-1.32, P < .001), 1 year (RR: 1.24, CI 1.15-1.33, P < .001), and at 3 years (RR: 1.29, CI 1.21-1.38, P < .001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. CONCLUSIONS: A higher rate of progression of PDR and risk of new-onset DME was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision-threatening complications.

Retinal Detachment After Macular Hole Repair in Alport Syndrome.

Alport syndrome is characterized by type IV collagen network disruptions leading to renal, auditory, and ocular manifestations. This case report details a 24-year-old man with Alport syndrome who developed a rhegmatogenous retinal detachment following macular hole repair. The patient underwent a successful vitrectomy and internal limiting membrane peel for macular hole repair but returned with vision loss due to retinal detachment five weeks later, which necessitated a combined scleral buckle and vitrectomy. This is the first case describing rhegmatogenous retinal detachment post-macular hole repair in Alport syndrome. [Ophthalmic Surg Lasers Imaging Retina 2024;55:289-292.].

Association of Ocular Manifestations of Marfan Syndrome With Cardiovascular Complications.

PURPOSE: To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications. DESIGN: Retrospective cohort study. METHODS: The TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of more than 119 million patients, was used to identify patients diagnosed with Marfan syndrome. Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching. Odds ratios and 95% CIs were calculated for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome. RESULTS: A total of 19,105 patients were identified who were diagnosed with Marfan disease without ocular manifestations, and an additional 3887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR 2.035; P < .0001), mitral valve prolapse (OR 2.725; P < .0001), tricuspid valve disorders (OR 2.142; P < .0001), cardiac arrhythmias (OR 1.836; P < .0001), and all cardiovascular outcomes combined (OR 2.194; P < .0001). CONCLUSIONS: In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.

Acute Subretinal Fluid Accumulation Induced by Futibatinib Therapy for Malignant Metastatic Breast Cancer.

Futibatinib is an irreversible inhibitor of fibroblast growth factor receptors and is currently the subject of phase II clinical trials for the treatment of metastatic carcinomas. We report a case of a 59-year-old woman with metastatic malignant breast cancer who developed acute symptomatic subretinal fluid (SRF) accumulation after two weeks of futibatinib therapy. The SRF resolved within two weeks after futibatinib cessation. The medication was subsequently restarted at a lower dose, and SRF recurred within two weeks. To our knowledge, this is the first case depicting rapidly reversible SRF accumulation with the use of futibatinib in a real-world clinical setting. [Ophthalmic Surg Lasers Imaging Retina 2024;55:109-111.].

Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death After Retinal Vein Occlusion.

PURPOSE: To examine rates of stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death in patients after retinal vein occlusion (RVO) compared to controls. DESIGN: Retrospective cohort study. METHODS: An aggregated electronic health records research network, TriNetX, was used to identify patients with diagnosis of RVO and a control group of patients with cataract. Patients were excluded if they had history of stroke, MI, DVT, or PE within 2 years of diagnosis of RVO or cataract. Propensity score matching was performed to control for baseline demographics and medical comorbidities. Main outcomes included relative risk (RR) of death, stroke, MI, DVT, and PE after RVO compared to those in matched controls. RESULTS: A total of 45,304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 year (RR = 1.30, P < .01), 5 years (RR = 1.22, P < .01), and 10 years (RR = 1.08, P < .01). There was elevated risk of stroke at 1 year (RR = 1.61, P < .01), 5 years (RR = 1.31, P < .01), and 10 years (RR = 1.18, P < .01). There was elevated risk of MI at 1 year (RR = 1.26, P < .01) and 5 years (RR = 1.13, P < .01), but not at 10 years (RR = 1.06, P = .12). There was mildly elevated risk of DVT at 1 year (RR = 1.65, P < .01) but not at 5 years (RR = 0.94, P = .94) or 10 years (RR = 1.05, P = .37). There was no elevated risk of PE at 1 year (RR = 0.98, P = 0.80), 5 years (RR = 0.95, P = .42), or 10 years (RR = 0.85, P =.40). CONCLUSIONS: There is an increased rate of death, stroke, and MI after RVO compared to those in matched controls. We emphasize the need for long-term systemic evaluation after RVO.

Risk of Stroke, Myocardial Infarction, and Death After Retinal Artery Occlusion.

Importance: Patients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear. Objective: To determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort. Design, Setting, and Participants: This retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract. Exposure: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract. Main Outcomes and Measures: Rate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls. Results: There were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003). Conclusions and Relevance: This study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.

Biobanking of Human Aqueous and Vitreous Liquid Biopsies for Molecular Analyses.

A critical challenge in translational research is establishing a viable and efficient interface between patient care in the operating room (OR) and the research laboratory. Here, we developed a protocol for acquiring high-quality liquid biopsies for molecular analyses from the aqueous humor and the vitreous from patients undergoing eye surgery. In this workflow, a Mobile Operating Room Lab Interface (MORLI) cart equipped with a computer, a barcode scanner, and lab instruments, including onboard cold storage, is used to obtain and archive human biological samples. A web-based data privacy-compliant database enables annotating each sample over its lifetime, and a cartesian coordinate system allows tracking each barcoded specimen in storage, enabling quick and accurate retrieval of samples for downstream analyses. Molecular characterization of human tissue samples not only serves as a diagnostic tool (e.g., to distinguish between infectious endophthalmitis and other non-infectious intraocular inflammation) but also represents an important component of translational research, allowing the identification of new drug targets, development of new diagnostic tools, and personalized therapeutics.

Photographic Gel Artifact Simulating International Classification of Retinopathy of Prematurity Notch: Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) Report no. 16.

PURPOSE: To report a series of fundus photographs taken for retinopathy of prematurity (ROP) screening that contain artifacts with imaging characteristics mimicking a notch, a recently refined classification metric in the International Classification of Retinopathy of Prematurity, third edition. DESIGN: Retrospective case series. PARTICIPANTS: Infants requiring ROP screening in neonatal intensive care units from the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) and TeleROP telemedicine screening programs. METHODS: Preterm infants meeting ROP examination criteria were screened with 130° wide-angle imaging systems. The images were taken by a trained nurse in the neonatal intensive care unit and transferred to an ROP specialist using a Health Insurance Portability and Accountability Act-compliant picture archiving and communication system for interpretation. MAIN OUTCOME MEASURES: Presence of an artifact that appeared consistent with a notch. RESULTS: We identified a total of 17 cases in ROP screening with artifact findings that had imaging characteristics similar to a notch. The artifactual appearance of the pseudo-notch was created by the camera illumination system within the gel-lens interface when the lens was not well apposed to the cornea. In telemedicine screening for ROP, we present fundus images of eyes with a pseudo-notch appearance; review of overlapping images can help differentiate between notch and artifact. CONCLUSIONS: Pediatric retinal specialists need to be aware that artifacts play a confounding role in screening for ROP, that can be mitigated through the use of overlapping and redundant images. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Evaluating the Effect of Hypoglycemic Agents on Diabetic Retinopathy Progression.

BACKGROUND AND OBJECTIVE: Newer hypoglycemics such as dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists have been increasingly used in diabetes. This study aimed to assess the relationship between usage of these hypoglycemic agents and effect on diabetic retinopathy (DR). MATERIALS AND METHODS: Using the Vestrum Health Retina Database, patients with DR with 1 year follow-up after use of a hypoglycemic agent were included and stratified by agent, including no pharmacotherapy. RESULTS: Of 60,649 eyes, in 1 year after hypoglycemic agent usage, progression rates from severe nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) were the following: DPP-4 (17%), SGLT-2 (12%), GLP-1 (21%), metformin (18%), and none (20%). Progression rates from moderate NPDR to severe NPDR or PDR were the following: DPP-4 (11%), SGLT-2 (10%), GLP-1 (11%), metformin (10%), none (13%). Progression rates from mild NPDR to moderate/severe NPDR or PDR were the following: DPP-4 (6%), SGLT-2 (9%), GLP-1 (9%), metformin (7%), and none (10%). CONCLUSIONS: Within a large real-world database, patients prescribed GLP-1 agonists were found to have DR progression rates comparable to those of patients receiving no hypoglycemic agents. [Ophthalmic Surg Lasers Imaging Retina 2023; 54(3):158-165.].

Visualization of retinal breaks on ultra-widefield fundus imaging using a digital green filter.

PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.

Acute Syphilitic Posterior Placoid Chorioretinitis With Subfoveal Choroidal Neovascularization Managed With Anti-VEGF Therapy.

Purpose: We describe the development and management of choroidal neovascularization (CNV) in a patient with acute syphilitic posterior placoid chorioretinitis (ASPPC). Methods: A retrospective case review is presented. Results: A 66-year-old man presented with unilateral blurry vision. He had a history of systemic syphilis infection twice, the last diagnosed 15 years before presentation and treated with intravenous ceftriaxone, resulting in seroreversion of an initially positive rapid plasma reagin (RPR). Examination revealed ASPPC with subfoveal CNV. Repeat testing revealed an RPR titer of 1:16 384. He was treated with 6 monthly intravitreal injections of bevacizumab and systemic antibiotics, resulting in resolution of his ASPPC and regression of his CNV. Conclusions: CNV is a rare complication of ASPPC. Multimodal imaging can be useful to suggest the diagnosis, and prompt treatment with systemic antibiotics and intravitreal anti-vascular endothelial growth factor agents can lead to resolution of ASPPC and regression of CNV, respectively.

The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration.

PURPOSE: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN: Retrospective cohort study. PARTICIPANTS: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES: Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001). CONCLUSIONS: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity.

Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.