Karen Wai, MD

All Publications

• Glaucoma tube shunt surgery with repeat penetrating keratoplasty in an aphakic patient. American journal of ophthalmology case reports Chiang, B., Wai, K., Naranjo, A., Smith, S., Rose-Nussbaumer, J., Liu, W. W. 2024; 36: 102145

  Abstract

  We present a complicated case of mixed mechanism glaucoma in the setting of failed corneal transplant and aphakia. The patient was a 54-year old male with HLA B27 uveitis and prior open globe injury. He was left aphakic after cataract extraction and had a subsequent corneal transplant for bullous keratopathy. Due to elevated intraocular pressure in the setting of a failed corneal graft, the decision was made to insert a pars plana tube shunt and perform repeat penetrating keratoplasty as a combined case with the glaucoma, cornea, and retina services. We illustrate the surgical steps and decision making and in this complex case.

  View details for DOI 10.1016/j.ajoc.2024.102145

  View details for PubMedID 39263687

  View details for PubMedCentralID PMC11388665

• Reply to Comment on Ophthalmic Immune-Related Adverse Events and Association with Survival: Results from a Real-World Database. American journal of ophthalmology Quiruz, L., Yavari, N., Kikani, B., Gupta, A. S., Wai, K. M., Kossler, A. L., Ludwig, C., Koo, E. B., Rahimy, E., Mruthyunjaya, P. 2024

  View details for DOI 10.1016/j.ajo.2024.11.001

  View details for PubMedID 39528009

• Use of Artificial Intelligence-Based Detection of Diabetic Retinopathy in the US. JAMA ophthalmology Shah, S. A., Sokol, J. T., Wai, K. M., Rahimy, E., Myung, D., Mruthyunjaya, P., Parikh, R. 2024

  View details for DOI 10.1001/jamaophthalmol.2024.4493

  View details for PubMedID 39480408

• Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration. JAMA ophthalmology Alsoudi, A. F., Wai, K. M., Koo, E., Mruthyunjaya, P., Rahimy, E. 2024

  Abstract

  Curcuma-based nutritional supplements (CBNS) are natural anti-inflammatory and antioxidant agents that may confer benefits against age-related macular degeneration (AMD).To examine the association between the use of CBNS and the risk of development or progression of AMD.This was a retrospective cohort study with data collection in June of 2024. Data were gathered from the aggregated electronic health records research network, TriNetX (Cambridge, Massachusetts). Patients without AMD were included in the study before propensity score matching (PSM); these included those taking and not taking CBNS. Patients with no history of AMD were stratified by instances of CBNS prescription records. Patients with a history of early nonexudative AMD stratified by instances of CBNS prescription records were also identified. PSM was performed to control for baseline demographics and medical comorbidities.Patients were stratified by whether or not they were taking CBNS using RxNorm (National Library of Medicine) codes.Relative risk (RR) of developing nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requiring intravitreal anti-vascular endothelial growth factor (VEGF) therapy.A total of 66 804 patients (mean [SD] age, 64.9 [10.1] years; 44 124 female [66.1%]) taking CBNS and 1 809 440 patients (mean [SD] age, 67.0 [9.5] years; 999 534 female [55.2%]) not taking CBNS were included in this study. Among patients without a history of AMD aged 50 years or older, CBNS use was associated with lower rates of developing nonexudative AMD (RR, 0.23; 95% CI, 0.21-0.26; P < .001), advanced nonexudative AMD or GA (RR, 0.11; 95% CI, 0.07-0.17; P < .001), exudative AMD (RR, 0.28; 95% CI, 0.24-0.32; P < .001), blindness (RR, 0.46; 95% CI, 0.36-0.59; P < .001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; 95% CI, 0.13-0.17; P < .001) when compared with matched patients not taking CBNS. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or GA (RR, 0.58; 95% CI, 0.41-0.81; P < .001) when compared with matched patients with early nonexudative AMD without a CBNS prescription record.Results of this cohort study suggest that a reduced risk of developing AMD or progression to later stages of AMD was associated with subsequent use of CBNS. Further investigation to validate these findings, safety, and potential pharmacoprotective mechanisms of CBNS in AMD are suggested.

  View details for DOI 10.1001/jamaophthalmol.2024.4400

  View details for PubMedID 39446346

• Risk of Intestinal Complications, Extraintestinal Morbidity, and Mortality in Patients with Crohn's Disease and Ocular Involvement. Ocular immunology and inflammation Alsoudi, A. F., Wai, K. M., Koo, E., McConnell, R. A., Pham, N. H., Do, B. K., Ludwig, C. A., Kossler, A. L., Mruthyunjaya, P., Rahimy, E. 2024: 1-8

  Abstract

  Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease.In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities.Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48-2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15-1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89-2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31-1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29-1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33-1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65-2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37-1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11-2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14-1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18-1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22-1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37-1.71, p < 0.001).Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement.

  View details for DOI 10.1080/09273948.2024.2413895

  View details for PubMedID 39401331

• Ophthalmic Immune-Related Adverse Events and Association with Survival: Results from a Real-World Database. American journal of ophthalmology Quiruz, L., Yavari, N., Kikani, B., Gupta, A. S., Wai, K. M., Kossler, A. L., Ludwig, C., Koo, E. B., Rahimy, E., Mruthyunjaya, P. 2024

  Abstract

  Assessing immune-related ocular toxicities from immune checkpoint inhibitors (ICIs) is crucial, though rare. This study, utilizing real-world data, examines the occurrence of ophthalmic immune-related adverse events (irAEs) after ICI treatment and their impact on overall survival.A retrospective cohort study METHODS: Data were obtained from TriNetX, an aggregated electronic health records database. Patients who developed ophthalmic irAEs within 1 year after the first instance of ICI therapy were included. Participants with defined ocular toxicities 6 months before ICI treatment were excluded. Subjects were paired with controls using propensity scores derived from demographics and cancer type. A Cox proportional hazard model was used to determine hazard ratios. A Kaplan-Meier survival function was evaluated with the log-rank test based on the development of ophthalmic irAEs in a 12-month landmark analysis.A cohort of 41,020 patients comprising 57.4% males with a mean age of 65.2±11.9 years was included. The five most prevalent ophthalmic irAEs in this cohort were dry eye syndrome (2%), conjunctivitis (0.87%), blepharitis (0.51%), anterior uveitis (0.39%), and keratitis (0.38%). Dry eye syndrome was the most common irAE among all ICI classes. Subjects taking CTLA-4 inhibitor plus PD-1 inhibitor and CTLA-4 inhibitors had higher rates of anterior uveitis (1.39% and 1.29%, respectively) than PD-1 inhibitors (0.27%) and PD-L1 inhibitors (0.14%) within 1 year after taking ICI. After a 12-month landmark analysis, there was a significant decreased chance of survival for the following categories: any ophthalmic irAE (HR, 1.37; 95% CI, 1.20-1.56; P < 0.0001), neuro-ophthalmic irAE (HR, 1.53; 95% CI, 1.09-2.14; P = 0.0124), and cornea and ocular surface irAE (HR, 1.34; 95% CI, 1.15-1.56; P < 0.0001).Ophthalmic irAEs involving the anterior segment are more frequent than the posterior segment, regardless of ICI class. Ophthalmic irAEs may also portend decreased survival. This insight could help guide clinicians aggressively manage irAEs and allow patients to continue ICI therapy despite having ocular issues.

  View details for DOI 10.1016/j.ajo.2024.08.044

  View details for PubMedID 39271090

• Reply to comment on: Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study. American journal of ophthalmology Wai, K. M., Mishra, K., Koo, E., Ludwig, C. A., Parikh, R., Mruthyunjaya, P., Rahimy, E. 2024

  View details for DOI 10.1016/j.ajo.2024.08.036

  View details for PubMedID 39241978

• Initial Therapy of Panretinal Photocoagulation vs Anti-VEGF Injection for Proliferative Diabetic Retinopathy. JAMA ophthalmology Alsoudi, A. F., Wai, K. M., Koo, E., Parikh, R., Mruthyunjaya, P., Rahimy, E. 2024

  Abstract

  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.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.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.Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP.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.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.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.

  View details for DOI 10.1001/jamaophthalmol.2024.3283

  View details for PubMedID 39207799

  View details for PubMedCentralID PMC11362971

• Risk of ocular neovascular conversion and systemic bleeding complications in patients with AMD on DOACs or Warfarin. Ophthalmology Alsoudi, A. F., Koo, E., Wai, K., Mruthyunjaya, P., Rahimy, E. 2024

  Abstract

  Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin.Retrospective cohort study.The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM).TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities.Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy.Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years.Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs.

  View details for DOI 10.1016/j.ophtha.2024.07.034

  View details for PubMedID 39116948

• Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications. American journal of ophthalmology Rahimy, E., Koo, E. B., Wai, K. M., Ludwig, C. A., Kossler, A. L., Mruthyunjaya, P. 2024

  Abstract

  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).Retrospective cohort study.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.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).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.

  View details for DOI 10.1016/j.ajo.2024.07.021

  View details for PubMedID 39089360

• Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review. Vision (Basel, Switzerland) Zhao, C. S., Wai, K., Koo, E. B., Rahimy, E., Mruthyunjaya, P., Mahajan, V. B., DeBoer, C. M. 2024; 8 (3)

  Abstract

  We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies.A 70-year-old male with acute myeloid leukemia who had recently undergone a bone marrow transplant noted bilateral floaters and decreased vision. He was found to have bilateral Fusarium endophthalmitis, with subsequent evidence of fungemia and fusariosis in his skin and joints. Despite aggressive local and systemic treatment, he succumbed to the disease. Endophthalmitis was initially stabilized with pars plana vitrectomy and intravitreal amphotericin and voriconazole until the patient transitioned to comfort measures. A review of 31 cases demonstrates that outcomes are poor and that the disease must be treated aggressively, often both systemically and surgically.This case highlights the recalcitrance of Fusarium bacteremia and Fusarium endophthalmitis.

  View details for DOI 10.3390/vision8030044

  View details for PubMedID 39051230

• Progression to Pars Plana Vitrectomy in Patients With Proliferative Diabetic Retinopathy. JAMA ophthalmology Alsoudi, A. F., Wai, K. M., Koo, E., Parikh, R., Mruthyunjaya, P., Rahimy, E. 2024

  Abstract

  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.

  View details for DOI 10.1001/jamaophthalmol.2024.1844

  View details for PubMedID 38842828

• Geographic Atrophy Natural History Versus Treatment: Time to Fovea OPHTHALMIC SURGERY LASERS & IMAGING RETINA Zhang, C., Kahan, E., Begaj, T., Friedman, S. M., Deobhakta, A., Heyang, M., Shen, L., Moshfeghi, D., Wai, K., Parikh, R. 2024: 1-10

  Abstract

  The Food and Drug Administration recently approved treatments of geographic atrophy (GA). Our study aims to quantify the time for a lesion to reach the central fovea based on reduction of GA growth rates from therapeutics compared to the natural history.A previously published study calculates local border expansion rate of GA lesions at varying retinal eccentricities. In this study, we use these rates to model GA expansion toward the fovea and the effects of treatments that reduce growth in GA area by 15% to 45% on lesions of varying sizes with posterior margin 250, 500, 750, 1000, 1250, 1500, and 3000 µm from the fovea.Lesions with an area 8 mm2 and posterior edge 500 µm from the fovea will reach the fovea in 5.08 years with no treatment, but the same lesions will reach the fovea in 5.85, 6.52, 7.36, and 8.46 years with a treatment that reduces growth in GA area by 15%, 25%, 35%, and 45%, respectively.Distance of the posterior edge of the lesion was the primary factor in GA growth toward the fovea, and lesion size only minimally affects growth rates of GA. Based on the efficacy of current and future therapeutics and distance of GA to the fovea, our study provides the marginal time benefit of treatment to guide patients and clinicians, placing both the natural history of GA and the effects of current and future treatments into clinical context. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

  View details for DOI 10.3928/23258160-20240418-01

  View details for Web of Science ID 001322740400001

  View details for PubMedID 38917392

• Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study. American journal of ophthalmology Wai, K. M., Mishra, K., Koo, E., Ludwig, C. A., Parikh, R., Mruthyunjaya, P., Rahimy, E. 2024

  Abstract

  PURPOSE: To examine the effects of GLP-1 agonists compared to SGLT-2 inhibitors on diabetic retinopathy.DESIGN: Retrospective clinical cohort study using TriNetX (Cambridge, MA, USA), a federated electronic health records network comprising multiple healthcare organizations.METHODS: Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of non-proliferative diabetic retinopathy and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with history of proliferative diabetic retinopathy prior to initiation of treatment were excluded. Rate of progression to proliferative diabetic retinopathy and rate of development of diabetic macular edema 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 non-proliferative diabetic retinopathy. Main outcomes included rate and relative risk of progression to proliferative diabetic retinopathy and risk of diabetic macular edema 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 year and 3 years after initiation of therapy, a higher rate of progression of proliferative diabetic retinopathy was noted (RR: 1.26, CI 1.04-1.51, p=0.017 at 1 year, RR: 1.284, CI 1.1-1.499, p=0.002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of diabetic macular edema noted at 3 months (RR: 1.192, CI 1.059-1.276, p=0.002), 6 months (RR: 1.22, CI 1.13-1.32, p<0.001), 1 year (RR: 1.24, CI 1.15-1.33, p<0.001), and at 3 years (RR: 1.29, CI 1.21-1.38, p<0.001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort.CONCLUSIONS: A higher rate of progression of proliferative diabetic retinopathy and risk of new-onset diabetic macular edema 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.

  View details for DOI 10.1016/j.ajo.2024.04.010

  View details for PubMedID 38636788

• Recovery of Vision in Open Globe Injury Patients with Initial No Light Perception Vision. Ophthalmology. Retina Sherif, N. A., Hoyek, S., Wai, K., Makhoul, K. G., Bitar, R., Teiger, M., Lorch, A. C., Patel, N. A., Armstrong, G. W. 2024

  Abstract

  OBJECTIVE OR PURPOSE: To identify clinical characteristics of injured eyes associated with visual recovery in patients with open globe injuries (OGI) and presenting with no light perception (NLP) vision.DESIGN: Retrospective chart review.SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: All patients presenting to Massachusetts Eye and Ear with OGI and NLP vision from January 1999 to March 2022.METHODS, INTERVENTION, OR TESTING: Manual data extraction to collect patient demographic characteristics, pre-operative, intraoperative, and post-operative characteristics of OGI injury, laceration versus rupture, history of intraocular surgery, time from injury to repair, timing of vitrectomy, lensectomy, choroidal drainage, and silicone oil placement, visual acuity (VA) at last follow-up, and subsequent B-scan ultrasound findings of retinal detachment, choroidal hemorrhage, vitreous hemorrhage, and disorganized intraocular contents. Patients with more than one week of follow-up and a documented VA at most recent follow-up were included. Exclusion criteria included age less than 10 years. Multivariable regression was performed.MAIN OUTCOMES: VA recovery defined as light perception or better in patients with OGI and initial NLP vision.RESULTS: 147 eyes with NLP vision after OGI were included. 25 (17%) eyes regained vision at last follow-up. The majority of patients recovered light perception vision (n=15, 60%) followed by 20/500 or better (n=5, 20%), hand motion (n=3, 12%), and count fingers (n=2, 8%). Most injuries were zone III (n=102, 69%) and presented with rupture (n=127, 86%). The mean time from OGI to surgical repair was 0.85 ± 1.7 days. B-scan was obtained in 104 (71%) cases. Pars plana vitrectomy was performed in 9 eyes (6%) with NLP at time of vitrectomy. Disorganized intraocular contents on B-scan (OR=0.170, 95%CI: 0.042-0.681, P=0.012) was the only clinical variable significantly associated with visual recovery, corresponding to a lack of visual improvement.CONCLUSION: Recovery of vision in OGI with NLP vision at presentation cannot be predicted based on presenting clinical features. B-scan findings of disorganized intraocular contents after initial OGI repair was the only factor negatively associated with vision recovery in this patient population. Therefore, all eyes presenting with an OGI and NLP vision should undergo primary repair in hopes of subsequent visual recovery.

  View details for DOI 10.1016/j.oret.2024.04.010

  View details for PubMedID 38636901

• Association of ocular manifestations of Marfan syndrome with cardiovascular complications. American journal of ophthalmology Tran, E. M., Wai, K. M., Kossler, A. L., Mruthyunjaya, P., Rahimy, E., Koo, E. B. 2024

  Abstract

  To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications.retrospective cohort study METHODS: Setting: TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of over 119 million patients.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 ratio and 95% confidence intervals for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome.19,105 patients were identified that were diagnosed with Marfan disease without ocular manifestations, and an additional 3,887 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 2,465 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=<0.0001), mitral valve prolapse (OR=2.725; p= p=<0.0001), tricuspid valve disorders (OR=2.142; p=<0.0001), cardiac arrhythmias (OR=1.836; p=<0.0001), and all cardiovascular outcomes combined (OR=2.194; p=<0.0001).In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.

  View details for DOI 10.1016/j.ajo.2024.02.023

  View details for PubMedID 38403098

• Acute Subretinal Fluid Accumulation Induced by Futibatinib Therapy for Malignant Metastatic Breast Cancer OPHTHALMIC SURGERY LASERS & IMAGING RETINA Chhoy, B., Wai, K. M., Leng, T. 2024; 55 (2): 109-111

  Abstract

  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:XX-XX.].

  View details for DOI 10.3928/23258160-20231205-02

  View details for Web of Science ID 001178161800006

  View details for PubMedID 38408224

• Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Post-operative Proliferative Vitreoretinopathy. Ophthalmology Mammo, D. A., Wai, K., Rahimy, E., Pan, C. K., Srivastava, S. K., Mruthyunjaya, P. 2024

  Abstract

  PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) with risk of post-operative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair.DESIGN: Retrospective population-based cohort study PARTICIPANTS: Patients ≥ 18 years who underwent initial RD repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology (CPT) 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003 - March 1, 2023.METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Statistical Classification of Diseases (ICD)-10 codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2), and CPT codes for secondary surgery including complex RD repair (67113) was determined. Proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) patients were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) was used to match for age, sex, and race.MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in KHF cohort versus non-KHF cohort.RESULTS: Among patients with CPT 67108, 1,061 patients in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (SD) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (p=0.00, OR 3.2; 95% CI, 2.13-4.71). 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (p=0.008; OR 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF vs non-KHF cohort (9.0% vs 4.2%, p < 0.01; OR 2.28 (1.64-3.16).CONCLUSION: A dermatologic history of keloids, hypertrophic scarring, or fibrosis may be a risk factor for proliferative vitreoretinopathy after retinal detachment repair.

  View details for DOI 10.1016/j.ophtha.2024.01.032

  View details for PubMedID 38296203

• Risk of Stroke, Myocardial Infarction, and Death After Retinal Artery Occlusion. JAMA ophthalmology Wai, K. M., Knapp, A., Ludwig, C. A., Koo, E., Parikh, R., Rahimy, E., Mruthyunjaya, P. 2023

  Abstract

  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.

  View details for DOI 10.1001/jamaophthalmol.2023.4716

  View details for PubMedID 37883068

• Biobanking of Human Aqueous and Vitreous Liquid Biopsies for Molecular Analyses. Journal of visualized experiments : JoVE Wolf, J., Chemudupati, T., Kumar, A., Rasmussen, D. K., Wai, K. M., Chang, R. T., Montague, A. A., Tang, P. H., Bassuk, A. G., Dufour, A., Mruthrunjaya, P., Mahajan, V. B. 2023

  Abstract

  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.

  View details for DOI 10.3791/65804

  View details for PubMedID 37747194

• Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death after Retinal Vein Occlusion. American journal of ophthalmology Wai, K. M., Ludwig, C. A., Koo, E., Parikh, R., Mruthyunjaya, P., Rahimy, E. 2023

  Abstract

  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.Retrospective cohort study.An aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), 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 matched controls.45304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 (RR: 1.30, p<0.01), 5 (RR: 1.22, p<0.01), and 10 years (RR:1.08, p<0.01). There was elevated risk of stroke at 1 (RR:1.61, p<0.01), 5 (RR:1.31, p<0.01), and 10 years (RR: 1.18, p<0.01). There was elevated risk of MI at 1 (RR:1.26, p<0.01) and 5 years (RR:1.13, p<0.01), but not at 10 years (RR:1.06, p=0.12). There was mildly elevated risk of DVT at 1 year (RR: 1.65, p<0.01), but not at 5 (RR: 0.94, p=0.94) or at 10 years (RR: 1.05, p=0.37), There was no elevated risk of PE at 1 (RR: 0.98, p=0.80), 5 (RR: 0.95, p=0.42), or 10 years (RR: 0.85, p=0.40).There is an increased rate of death, stroke, and MI after RVO compared to matched controls. We emphasize the need for long term systemic evaluation after RVO.

  View details for DOI 10.1016/j.ajo.2023.08.022

  View details for PubMedID 37660963

• Photographic Gel Artifact Simulating International Classification of Retinopathy of Prematurity Notch: Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) Report no. 16. Ophthalmology. Retina Wai, K. M., Moshfeghi, D. M. 2023; 7 (8): 732-736

  Abstract

  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.

  View details for DOI 10.1016/j.oret.2023.04.013

  View details for PubMedID 37548218

• Effect of Next Generation Oral Hypoglycemic Agents on Diabetic Retinopathy Progression: A National Cohort Study Wai, K., Ahluwalia, A., Abrant, A., Ludwig, C., Parikh, R., Mruthyunjaya, P., Rahimy, E. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758307286

• Evaluating the Effect of Hypoglycemic Agents on Diabetic OPHTHALMIC SURGERY LASERS & IMAGING RETINA Wai, K. M., Saroj, N., Boucher, N., Aggarwal, N., Ho, A. C., Rahimy, E. 2023; 54 (3): 158-165

  Abstract

  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).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.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%).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.].

  View details for Web of Science ID 000975451300001

  View details for PubMedID 36944068

• Acute Syphilitic Posterior Placoid Chorioretinitis With Subfoveal Choroidal Neovascularization Managed With Anti-VEGF Therapy. Journal of vitreoretinal diseases Wai, K. M., Gong, D., Rodriguez, M., Cunningham, E. T., Vavvas, D. G., Eliott, D. 2022; 6 (3): 246-250

  Abstract

  We describe the development and management of choroidal neovascularization (CNV) in a patient with acute syphilitic posterior placoid chorioretinitis (ASPPC).A retrospective case review is presented.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.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.

  View details for DOI 10.1177/24741264211057663

  View details for PubMedID 35967270

  View details for PubMedCentralID PMC9368478

• Astrocytic TGF-beta Signaling Limits Inflammation and Reduces Neuronal Damage during Central Nervous System Toxoplasma Infection JOURNAL OF IMMUNOLOGY Cekanaviciute, E., Dietrich, H. K., Axtell, R. C., Williams, A. M., Egusquiza, R., Wai, K. M., Koshy, A. A., Buckwalter, M. S. 2014; 193 (1): 139-149

  Abstract

  The balance between controlling infection and limiting inflammation is particularly precarious in the brain because of its unique vulnerability to the toxic effects of inflammation. Astrocytes have been implicated as key regulators of neuroinflammation in CNS infections, including infection with Toxoplasma gondii, a protozoan parasite that naturally establishes a chronic CNS infection in mice and humans. In CNS toxoplasmosis, astrocytes are critical to controlling parasite growth. They secrete proinflammatory cytokines and physically encircle parasites. However, the molecular mechanisms used by astrocytes to limit neuroinflammation during toxoplasmic encephalitis have not yet been identified. TGF-β signaling in astrocytes is of particular interest because TGF-β is universally upregulated during CNS infection and serves master regulatory and primarily anti-inflammatory functions. We report in this study that TGF-β signaling is activated in astrocytes during toxoplasmic encephalitis and that inhibition of astrocytic TGF-β signaling increases immune cell infiltration, uncouples proinflammatory cytokine and chemokine production from CNS parasite burden, and increases neuronal injury. Remarkably, we show that the effects of inhibiting astrocytic TGF-β signaling are independent of parasite burden and the ability of GFAP(+) astrocytes to physically encircle parasites.

  View details for DOI 10.4049/jimmunol.1303284

  View details for Web of Science ID 000338438900019

  View details for PubMedCentralID PMC4075480