Cigdem Yasar
Postdoctoral Scholar, Ophthalmology
Stanford Advisors
-
Quan Dong Nguyen, Postdoctoral Research Mentor
-
Andrea Kossler, Postdoctoral Faculty Sponsor
All Publications
-
Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.
Ocular immunology and inflammation
2022: 1-7
Abstract
To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies.Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score.Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases.IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.
View details for DOI 10.1080/09273948.2022.2126374
View details for PubMedID 36542775
-
Bilateral retinal vasculitis associated with cold agglutinin disease treated with obinutuzumab and infliximab.
American journal of ophthalmology case reports
2022; 28: 101752
Abstract
To describe the clinical course and management of a patient with bilateral retinal vasculitis associated with cold agglutinin disease (CAD) treated with obinutuzumab and infliximab.A 69-year-old Hispanic woman was referred to a tertiary Uveitis Clinic with progressively worsening blurry vision, right eye (OD) worse than left eye (OS). Past ocular history was significant for epiretinal membranes in both eyes (OU). Past medical history was notable for non-specific joint disease, primarily affecting her knees bilaterally, and pulmonary symptoms (e.g., dyspnea, productive cough) of unclear etiologies one year before presentation. She had been evaluated by rheumatologists and pulmonologists and was placed on low doses of prednisone and methotrexate. Upon examination, her visual acuity was 20/40 in OD and 20/25 in OS. Anterior segment exam was unremarkable with no cell or flare in OU. Dilated fundus examination was notable for 0.5+ vitreous haze in OU and mild vessel attenuation in OU. Wide-angle fluorescein angiography (FA) revealed mild bilateral periphery peri-vasculature leakage in OU. Initial blood evaluations revealed decreased hematocrit, and positive anti-nuclear antibody. Her peripheral smear disclosed 3+ agglutination. She was initially treated with mycophenolate mofetil 1000 mg twice daily and prednisone 20 mg then referred to hematology. Further work up revealed high-titer cold agglutinin and positive thermal amplitude screen at 30 °C. Bone marrow examination demonstrated a chronic lymphocytic leukemia (CLL)-like monoclonal B-cell lymphocytosis. Anti-CD20 monoclonal antibody therapy with obinutuzumab was started in an effort to treat the underlying CLL clone and address the associated ocular vasculitis related to CAD. Three months later, after eight cycles of obinutuzumab, the patient's best- corrected visual acuity (BCVA) continued to be stable at 20/30 in OD and 20/20 in OS. However, FA showed persistent diffuse perivascular leakage. Intravenous infliximab with concurrent intravenous methylprednisolone infusions were started. After two cycles of treatment, FA showed significantly improved perivascular leakage. Visual acuity remained stable at 20/25 in OU.Ocular involvement in CAD is rare. The index case is the first report of retinal vasculitis in a patient with CAD. Our report not only describes the unique course of CAD-related retinal vasculitis, but also introduces and underscores a successful therapeutic plan.
View details for DOI 10.1016/j.ajoc.2022.101752
View details for PubMedID 36425783
View details for PubMedCentralID PMC9679462
-
Multifocal electroretinographic findings in angiographic macular leakage in the setting of intermediate, posterior, or panuveitis.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologie
2022
Abstract
To evaluate the functional implications of angiographic macular leakage without the presence of intraretinal fluid on optical coherence tomography (OCT) in eyes with intermediate, posterior, or panuveitis.Retrospective study on patients with a diagnosis of intermediate, posterior, or panuveitis. Patients who had fluorescein angiography, OCT, and multifocal electroretinography (mfERG) within a predetermined time frame were included. Demographic and clinical data including types of ocular inflammation and best-corrected visual acuity (BCVA), in addition to OCT, fluorescein angiography, and mfERG data were collected. The study cohort was divided into 2 groups based on the presence of angiographic macular leakage and macular edema (ME): group 1 (no ME and no macular leakage) and group 2 (presence of macular leakage without ME).A total of 29 patients (43 eyes) were included in the study, with 13 patients (17 eyes) in group 1 and 16 patients (26 eyes) in group 2. No statistically significant differences in age, sex, anterior-chamber cells, lens status, vitreous cells, vitreous haze, BCVA, or mean central subfoveal thickness were found between groups 1 and 2. All mfERG values, including N1 and P1 response densities and timings for rings 1-5, did not show any statistically significant difference between group 1 and 2. No correlation was found between either of BCVA or central subfoveal thickness and any of mfERG values for rings 1-3.In absence of ME, angiographic macular leakage in eyes with uveitis might not be associated with worse macular function when compared with eyes without angiographic macular leakage.
View details for DOI 10.1016/j.jcjo.2022.11.002
View details for PubMedID 36442516
-
Electroretinographic findings in retinal vasculitis.
The British journal of ophthalmology
2022
Abstract
To describe and correlate electroretinographic responses with clinical and angiographic findings in retinal vasculitis (RV).Medical records of patients with diagnosis of RV at a tertiary eye centre from December 2017 to May 2021 were reviewed. Cases in which fluorescein angiography (FFA) and full field electroretinography (ffERG) were done within 1 month were included. FFAs were graded according to the Angiography Scoring for Uveitis Working Group from 0 to 40, where 0 is normal. A novel ffERG grading system was implemented where individual waves were graded for timing and amplitude and general ffERG score was determined with 6 being a perfect score.20 patients (34 eyes) were included. Mean age was 43.9±19.8 years; 70% were female. Median best-corrected visual acuity was 0.8 (0.08-1). Mean FFA score was 12.6±6.5. Median general ffERG score was 5 (0-6). 68% and 91% of eyes had responses with general ffERG scores ≥5 and 4, respectively. Flicker timing was most commonly affected.FFA scores weakly correlated with delayed photopic cone b-wave and flicker timing (p=0.03 and 0.016, respectively). Vitreous haze moderately correlated with delayed cone b-wave timing (p<0.001), delayed flicker timing (p=0.002) and weakly correlated with lower flicker amplitude (p=0.03). Underlying systemic disease was associated with poor ffERG responses.In this study, RV was not frequently associated with severe global retinal dysfunction Higher FFA scores, and vitreous haze grading were weakly, but significantly, correlated with cone-generated ffERG responses.
View details for DOI 10.1136/bjo-2022-321716
View details for PubMedID 36130816
-
Posterior manifestations and longitudinal outcomes in TINU syndrome
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844437002261
-
Novel retinopathy in pediatric retinal vasculitis: long term follow up
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844437001051
-
Electroretinographic findings in retinal vasculitis
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302086
-
Correlation between Diopsys (R) NOVA fixed-luminance flicker phase and Diagnosys (R) flicker implicit time
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302077
-
Multifocal electroretinographic findings in eyes with posterior uveitis and angiographic macular leakage
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302088
-
Effect of Topical Bromfenac on Macular Thickness Changes after Vitrectomy or Phacovitrectomy for Epiretinal Membrane
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844437002267
-
Repeatability of electroretinogram measurements
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302074
-
Safety of Intravenous Methylprednisolone in Refractory and Severe Pediatric Uveitis.
Clinical ophthalmology (Auckland, N.Z.)
2022; 16: 1697-1706
Abstract
Purpose: To evaluate the safety of intravenous high-dose pulse methylprednisolone succinate (IVHDM) in the management of severe or refractory non-infectious pediatric uveitis.Methods: We reviewed all uveitis patients who were ≤16 years of age and who received IVHDM with a dose of ≥500 mg per day (1-3 days a month) for at least 3 months during their management at a tertiary care eye hospital.Results: Twenty pediatric patients with severe or refractory uveitis who received IVHDM were identified. Six patients received IVHDM either once, as a preoperative medication, or at a lower dose than 500 mg, and were excluded. The remaining 14 patients received IVHDM for at least 4 months. Age (mean±SD) was 11.9±2.4 years and 50% were female. Duration of treatment was 14.2±7.5 months. Thirteen patients received IVHDM in combination with other immunomodulatory therapy (IMT). Except for two outliers, IVHDM was given at a dose of 8-25 mg/kg per infusion. Three major adverse events (AEs) occurred in two patients: a single episode of bradycardia, compression fracture following minor trauma and adrenal insufficiency. The number of AEs (major and minor) strongly correlated with duration of treatment (p=0.004) and moderately correlated with the cumulative dose/weight (p=0.051). Weight gain was associated with the use of concomitant oral steroids and not with duration of treatment or cumulative dose.Conclusion: IVHDM may be a valid therapeutic option for aggressive/refractory pediatric uveitis. The reported AEs in this series can also be attributed to the concurrent IMT or the underlying disease itself.
View details for DOI 10.2147/OPTH.S366370
View details for PubMedID 35673349
-
Effect of Pupil Size on Fixed-Luminance Flicker Full-Field Electroretinogram Magnitude.
Clinical ophthalmology (Auckland, N.Z.)
2022; 16: 3733-3740
Abstract
Purpose: Diopsys NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device.Methods: Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses.Results: Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79V before dilation and 15.30±4.08V after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 V for every 1 mm increase in pupillary diameter.Conclusion: An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.
View details for DOI 10.2147/OPTH.S382207
View details for PubMedID 36389637
-
Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses.
Clinical ophthalmology (Auckland, N.Z.)
2022; 16: 1753-1771
Abstract
Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.
View details for DOI 10.2147/OPTH.S364200
View details for PubMedID 35685379
-
Structural changes of corneal epithelium in belantamab-associated superficial keratopathy using anterior segment optical coherence tomography.
American journal of ophthalmology case reports
2021; 23: 101133
Abstract
Purpose: To describe structural changes in corneal epithelium using anterior segment optical coherence tomography (AS-OCT) in two relapsed and refractory multiple myeloma (RRMM) patients with bilateral belantamab-associated superficial keratopathy (BASK).Observations case 1: A 56-year-old male who was diagnosed with RRMM and initiated on belantamab mafodotin, presented on day 42 (three weeks after the second infusion) with decreased pinhole visual acuity from 20/20 and 20/25 to 20/70 and 20/50 in the right eye and left eye, respectively. Slit-lamp examination revealed moderate superficial keratopathy with microcystic-like epithelial changes (MECs) in the paracentral cornea in both eyes. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions as well as increased thickness in the paracentral corneal epithelium with uninvolved central cornea. Given bilateral MECs, the third infusion was withheld, and then given on day 62 after five weeks of drug-free interval. Although MECs had improved on day 82, pinhole visual acuity remained at 20/50 and 20/40 in the right eye and the left eye. AS-OCT showed that hyperreflective lesions mostly resolved and corneal epithelial thickness returned to baseline, despite a slightly increased persisting heterogeneous signal intensity in the peripheral corneal epithelium in both eyes.Case 2: A 77-year-old male with RRMM was started on belantamab mafodotin infusions. His pinhole visual acuity decreased from 20/40 and 20/30 at baseline to 20/60 and 20/40 on day 41 (three weeks after the second infusion) in the right eye and left eye, respectively. Slit-lamp examination showed diffuse, moderate MECs in both eyes, which was more severe in the peripheral cornea. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions in the corneal epithelium, which are more severe in the right eye along with increased corneal epithelial thickness. Therefore, belantamab mafodotin was withheld.Conclusions and Impotance: AS-OCT objectively demonstrated structural changes such as signal intensity and thickness alterations with hyperreflective lesions in the corneal epithelium related to BASK. AS-OCT might be useful for clinicians to monitor ocular surface adverse events in RRMM patients receiving belantamab mafodotin and to adjust therapeutic plans for the patients.
View details for DOI 10.1016/j.ajoc.2021.101133
View details for PubMedID 34169181
-
Oral montelukast is associated with decreased odds of diabetic retinopathy
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100231
-
Effect of pupil size on fixed-luminance flicker full-field electroretinogram magnitude
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690760500607
-
Correlation between photoreceptor density in adaptive optics imaging with retinal structure and sensitivity in autoimmune retinopathy
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690760500009
-
Association of oral montelukast with reduced odds of developing neovascular age-related macular degeneration
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690760500276
-
Novel retinopathy identified in pediatric retinal vasculitis
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100499
-
Altered patient demography and increased complexity of ICD coding in uveitis over 10 years
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100498
-
Efficacy and safety of tocilizumab in the management of non-infectious retinal vasculitis
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100503
-
Structural and functional changes in non-paraneoplastic autoimmune retinopathy
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100493
-
Safety of intravenous high-dose pulse methylprednisolone succinate in the management of pediatric uveitis
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100497
-
Reperfusion of retinal ischemia in retinal occlusive vasculitis with nicotinic acid and infliximab in Adamantiades-Behcet's disease.
American journal of ophthalmology case reports
2021; 21: 101027
Abstract
To describe a case of ischemic retinal vasculitis in Adamantiades-Behcet disease (ABD) that demonstrated significant resolution of retinal ischemia following treatment with nicotinic acid and infliximab.Observations: A 12-year-old male with a history of recurrent oral ulcers, fevers, and failure to thrive was admitted to the hospital with fever, oral and perirectal mucositis, and poor oral intake one month before presentation to uveitis clinic. He was suspected to have ABD and was treated with three doses of intravenous (IV) methylprednisolone (30 mg/kg/day) which led to improvement in his systemic symptoms. One week after admission, he complained of decreased vision in both eyes (OU), during which he was found to have anterior uveitis in OU and was referred to the Uveitis Clinic. Upon examination, his visual acuity was 20/80 in OU. Intraocular pressures were within normal limits. Anterior chamber evaluation revealed 0.5+ cells and 1.5+ flare in OU. Posterior examination revealed pale optic nerve, sclerosis and vascular sheathing of retinal arteries, and collateral vessels in OU. Fluorescein angiography (FA) showed optic disc leakage and widespread retinal ischemia in OU. The patient was diagnosed with retinal occlusive vasculitis associated with ABD. He was initially treated with infliximab (5 mg/kg), systemic methylprednisolone, and mycophenolate mofetil. Three months later, his BCVA improved to 20/70 OU with slight improvement of retinal ischemia on FA. Nicotinic acid was added to his treatment regimen. Due to logistic challenges, he did not receive infliximab treatment during the subsequent three months. However, three months after beginning nicotinic acid therapy, FA revealed significant improvement of his retinal ischemia OU. Conclusion: To our knowledge, the index report is the first to show that nicotinic acid may improve retinal ischemia in vaso-occlusive retinal vasculitis and be an integral part of the treatment regimen of this sight-threatening condition.
View details for DOI 10.1016/j.ajoc.2021.101027
View details for PubMedID 33615039
-
Anti-interleukin-6 receptor therapy with tocilizumab for refractory pseudophakic cystoid macular edema.
American journal of ophthalmology case reports
2020; 20: 100881
Abstract
Purpose: To describe the clinical course of a patient with refractory pseudophakic cystoid macular edema treated with interleukin-6 receptor antagonist tocilizumab.Observations: An 80-year-old Caucasian man with past ocular history significant for glaucoma (right eye) and iritis presented with cystoid macular edema (CME) in the right eye (OD). His ocular surgery history was significant for cataract extraction with posterior chamber intraocular lenses in 1999 and YAG laser capsulotomy in 2014 in both eyes (OU). His medications at time of presentation included latanoprost and dorzolamide-timolol in OD for glaucoma, as well as prednisolone in OD for iritis. Upon examination, his visual acuity was 20/250 in OD and 20/20 in the left eye (OS). Intraocular pressure was 20mmHg in OD and 10mmHg in OS. Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed CME and a cup-to-disk ratio of 0.9 in OD and normal findings in OS. Initial spectral domain optical coherence tomography (SD-OCT) demonstrated intraretinal fluid in both outer and inner layers as well as mild subretinal fluid with an intact ellipsoid zone in OD. Fluorescein angiography revealed perifoveal leakage in OD. Laboratory evaluations, including infectious work-up, were unremarkable. While the patient's CME initially improved after initiation of therapy with topical prednisolone and oral acetazolamide, the CME later recurred after systemic acetazolamide was stopped due to intolerable side effects. Despite multiple therapeutic approaches, including topical and systemic corticosteroids (both oral and intravenous) and topical interferon alpha2b over the course of more than one year, the patient's visual acuity continued to worsen with increasing intra- and subretinal fluid in the macula. Due to the refractory CME, the patient was started on monthly infusions of anti-interleukin (IL)-6 receptor tocilizumab (8 mg/kg) with three days of methylprednisolone infusions (500 mg/day). After nine cycles of treatment, SD-OCT demonstrated restoration of normal foveal contour with complete resolution of CME.Conclusions and Importance: IL-6 inhibition with tocilizumab may be a safe and effective treatment for refractory CME. Further studies are needed to elucidate the nature and extent of therapeutic IL-6 inhibition in CME.
View details for DOI 10.1016/j.ajoc.2020.100881
View details for PubMedID 32875161
-
Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.
American journal of ophthalmology case reports
2020; 18: 100687
Abstract
To describe a case of unilateral retinal arteriolar occlusion following multiple intravitreal brolucizumab injections for neovascular age-related macular degeneration (nAMD).A 92-year-old Caucasian woman presented with blurry vision in her left eye (OS) after receiving the third dose of intravitreal brolucizumab. At the time of presentation, visual acuity (VA) was 20/40 in her right eye (OD) and had decreased from 20/150 to count finger (CF) at 1-foot OS. On examination, there was no evidence of active inflammation in the anterior chamber OU. Dilated fundus examination showed no vitritis in OD and 1+ vitreous cells OS, flame-shaped hemorrhage at the superior optic disc margin, and retinal whitening surrounding the proximal portion of the supero-temporal branch of the central retinal artery. There were drusen in OS and retinal pigment epithelial (RPE) changes in the maculae of OU. Intra-arteriolar greyish deposits were seen OS. Fluorescein angiography (FA) showed hyper-fluorescence in the maculae corresponding to fibrovascular pigment epithelial detachments (PED) OU. No peri-vascular leakage was noted OU. Delayed filling of multiple arterioles in early and late phases OS was observed on FA. The patient was diagnosed with retinal arteriolar occlusion associated with repeated intravitreal brolucizumab administrations.Retinal arteriolar occlusion with severe vision loss, possibly secondary to inflammatory responses, can occur after subsequent intravitreal brolucizumab injections, even if no inflammation occurred after initial administrations. Vaso-occlusive disease should be considered as a potential ocular complication, with acute as well as delayed onset, following intravitreal brolucizumab therapy.
View details for DOI 10.1016/j.ajoc.2020.100687
View details for PubMedID 32280811
View details for PubMedCentralID PMC7139151