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Purpose To describe two cases of catastrophic, bilateral retinal vascular occlusion following intravitreal (IVT) bevacizumab injection. Methods Case series. Main outcome measures included clinical and fluorescein angiography (FA) findings. Results Case 1 - A 65-year-old woman with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST) syndrome developed acute, severe, bilateral visual loss two weeks following bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and FA revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2 - An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left then right eye approximately three weeks following IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. FA showed diffuse venous leakage. Extensive testing revealed an elevated anti-nuclear antibody and mildly elevated anti-cardiolipin antibody. Conclusion Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion following treatment with IVT bevacizumab. The moderate to severe intraocular inflammation in both cases, and the contralateral involvement following unilateral IVT injection in Case 2, suggest a possible delayed immune-mediated mechanism.

PURPOSE To assess the relationship between best corrected visual acuity (BCVA) and central subfield optical coherence tomography (OCT) features in noninfectious uveitis (NIU)-related macular edema (ME). DESIGN Clinical cohort study from post hoc analysis of two phase 3 clinical trials' data. METHODS Correlation and longitudinal treatment analyses were performed. Of 198 patients with NIU, 134 received suprachoroidally administered CLS-TA (Clearside Biomedical, Inc. proprietary formulation of a triamcinolone acetonide injectable suspension) and 64 received sham, with 12.9% and 72% respectively receiving rescue therapy. RESULTS At baseline, mean BCVA progressively worsened with each ordinal drop in ellipsoid zone (EZ) integrity. Eyes with normal baseline EZ experienced greater 24-week change in BCVA compared to eyes with some degree of baseline EZ disruption (11.9 vs 9.4 letters, P=0.006). In contrast, eyes without central subfield cystoid spaces and/or central subfield SRF at baseline showed less improvement (5.5 letters or 9.5 letters, respectively) at 24 weeks, compared to those eyes with such OCT findings (13.7 letters, P = 0.012 or 17.2 letter, P

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.

PURPOSE To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT). METHODS Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography. RESULTS Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal. CONCLUSION Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.

PURPOSE To describe three patients with idiopathic multifocal choroiditis (MFC) who showed foci of foveal outer retinal hyperreflectivity on optical coherence tomography. METHODS Retrospective review of electronic health records and multimodal imaging from three patients with MFC. RESULTS Three consecutive white patients with MFC (two male and one female) presented with unilateral foveal outer retinal hyperreflectivity in the eye with active MFC. In all cases, the lesions persisted for at least 1 month. Optical coherence tomography demonstrated finger-like projections of hyperreflectivity extending from the retinal pigment epithelium and through disrupted interdigitation and ellipsoid zones into the outer nuclear layer, with some aspects of the lesions reaching the inner limiting membrane. Visual recovery varied in the three affected eyes. CONCLUSION Foveal outer retinal hyperreflectivity is a novel optical coherence tomography finding in eyes with active MFC. Additional studies will be required to address the prevalence and prognostic importance of foveal outer retinal hyperreflectivity.

To compare a nose-pivoted drop delivery device (NPDD) with traditional eye drop delivery in glaucoma subjects.Repeated-measures case series.Fifty glaucoma subjects (100 eyes) who reported difficulty self-administering eye drops.We compared eye drop delivery using a NPDD against traditional delivery techniques at baseline (baseline traditional) and after standardized teaching (post-teaching traditional). Subjects used a 1-to-10 scale (10 being easiest) to rate the ease of delivery with each technique and completed a satisfaction survey. Two graders used digital video to independently review eye drop delivery and recorded: (1) accurate placement: the eye drop reached the ocular surface; (2) no contact: no bottle tip contact against the ocular or periocular surface; and (3)number of eye drops dispensed. We defined primary success as accurate placement and no contact; secondary success as primary success with only 1 drop dispensed.We used logistic-transformed generalized estimating equation (GEE) regression to compare technique satisfaction, accuracy, no contact, and primary and secondary success. Number of drops dispensed was compared using a Cox model.Forty-seven of 50 subjects (94%) preferred the NPDD over traditional eye drop delivery. The mean score for ease of use was higher for the NPDD (8.9 ± 1.1) than baseline traditional (6.7 ± 2.1; P0.001) and post-teaching traditional (7.0 ± 2.0; P0.001). Forty-nine of 50 (98%) subjects thought the NPDD was comfortable to use and would recommend the device. The eye drop reached the ocular surface in a similar percentage of subjects (90%) with each method. The bottle tip contacted fewer eyes with the NPDD (10 eyes) than baseline traditional (33 eyes; P0.001) and post-teaching traditional (25 eyes; P = 0.009). The number of drops dispensed was lower with the NPDD (1.7 ± 1.2) than baseline traditional (2.2 ± 1.6; P = 0.017) and post-teaching traditional (2.4 ± 1.8; P = 0.006). The NPDD increased primary and secondary success of eye drop delivery (86% and 54%, respectively) compared to baseline traditional (66% [P = 0.001] and 28% [P0.001]) and post-teaching traditional (70% [P = 0.005] and 40% [P = 0.018]).Eye drop users preferred the NPDD over traditional eye drop delivery. The NPDD improved eye drop delivery success, reduced bottle tip contact, and decreased the number of eye drops wasted.

Purpose To provide a comprehensive review of rituximab use for the treatment of non-infectious/non-malignant orbital inflammation. Methods Review of literature through January 2021. Results Individual data was available for 167 patients with refractory non-infectious/non-malignant orbital inflammation who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (108/149, 72.5%) at a mean of 44.6 months following the diagnosis of orbital inflammation (range = 0 to 360 months; median = 13.7 months). Patients with non-infectious/non-malignant orbital inflammation either received prior treatment with corticosteroids only (27/122, 22.1%), or with one (31/122, 25.4%), two (25/122, 20.5%), or three or more (25/122, 20.5%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (80/144, 55.6%), followed by the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; 51/144, 35.4%). Various other off-label regimens were used infrequently (13/144, 9.0%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with orbital inflammation (146/166, 88.0%). Commonly treated diagnoses included granulomatosis with polyangiitis (99/167, 59.3%), IgG-4 related disease (36/167, 21.6%), and orbital inflammation of indeterminate cause (25/167, 15.0%). No side effects were reported in 83.3% (55/66) of cases. The most common RTX-induced adverse event was an infusion-related temporary exacerbation of orbital disease (4/66, 6.1%), which occurred prior to the routine use of systemic corticosteroids as pre-conditioning. Conclusions Overall, RTX appears to be both efficacious and well-tolerated as second- or third-line therapy for patients with non-infectious/non-malignant orbital inflammation.

To report an increasingly prevalent fundoscopic manifestation of syphilitic uveitis.Case report of a patient with acute retinal necrosis secondary to syphilis.A 48-year-old man presented with decreased vision, anterior segment inflammation, and a wedge-shaped retinal lesion in the superior periphery, with a diaphanous leading edge extending down towards the superior arcade. The patient was HIV+ and poorly compliant with therapy. The top three differential diagnoses were herpetic necrotizing retinitis, syphilis, and lymphoma. An extensive lab workup was positive for syphilis. The patient was treated with IV penicillin G and demonstrated improvement in visual acuity and exam.There have been an increasing number of reports of syphilis patients, especially in the population of men who have sex with men, who present with fundus findings similar to acute retinal necrosis. These findings include a characteristic ground glass, translucent appearance of unifocal or multifocal lesions, primarily affecting the inner retina and sometimes associated with co-localizing occlusive vasculitis. Treatment with IV penicillin G is warranted and has demonstrated good visual recovery.

Intravitreal (IVT) drug delivery now surpasses cataract surgery as the most commonly performed ophthalmic procedure worldwide. In 2020, nearly 23 million IVT injections were given globally,1 with m...

To describe the use of multimodal imaging to establish the diagnosis of Bartonella henselae-associated optic neuropathy in a patient who presented with a central scotoma without overt evidence of optic nerve involvement.Case report. Main outcome measures included clinical, optical coherence tomography, and fluorescein angiography findings.A 72-year-old woman presented with a three-day history of central scotoma in the left eye. Her examination was remarkable for faint exudation in the nasal macula of the left eye, but was otherwise normal for her age. Spectral domain optical coherence tomography of the macula revealed mild thickening of the papillomacular bundle with scattered small cystoid spaces and several intraretinal exudates, none of which were visible clinically. Fluorescein angiography revealed localized leakage of the inferotemporal optic disc. When prompted, the patient recalled being scratched multiple times by her two pet kittens. Serial testing showed rising anti-Bartonella henselae (B. henselae) IgG antibody titers to 1:1280, confirming the suspected diagnosis of B. henselae-associated optic neuropathy.and importance: Bartonella-associated optic nerve involvement can occur without overt evidence of optic disc swelling. Multimodal imaging can be used to suggest the diagnosis and support appropriate serologic testing.

Uveitis refers to a diverse group of several dozen disorders characterized and connected by the shared presence of intraocular inflammation.1,2 While the etiology of infectious uveitis is often cle...

Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Topic The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Tocilizumab (TCZ; Actemra®; Roche/Genentech in the US; Chugai Pharmaceutical Co. in Japan) is a recombinant, humanized monoclonal antibody directed against the interleukin-6 (IL-6) receptor and cur...

Purpose To report a case of Vogt-Koyanagi-Harada (VKH)-like uveitis followed by melanoma-associated retinopathy (MAR) with focal chorioretinal atrophy and subsequent choroidal neovascularization (CNV) in a patient with metastatic cutaneous melanoma. Observation A 68-year-old man with a history cutaneous melanoma presented with VKH-like uveitis. Work up revealed a pelvic mass, which was excised and found to be metastatic melanoma. Two years later, the patient developed MAR with focal chorioretinal atrophy and adjacent CNV. Conclusion and Importance: Patients with metastatic cutaneous melanoma can develop distinct and sequential paraneoplastic ocular complications. Onset of a VKH-like uveitis may be a good prognostic factor for survival in patients with metastatic cutaneous melanoma.

To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. Of the ...

Epstein-Barr Virus (EBV), also known as Human HerpesVirus-4 (HHV-4), is a γ-type herpesvirus with a global infection prevalence of over 95%.1,2 Infection, which occurs nasopharyngeally via either a...

To determine the prevalence and characteristics of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) in eyes with patchy atrophy because of pathologic myopia.Five hundred eyes of 253 patients with patchy atrophy were examined between 2014 and 2020 at the Advanced Clinical Center for Myopia. The main outcome measures included the prevalence and characteristics of active MFC/PIC lesions diagnosed by optical coherence tomography.Fifty-five of the 500 eyes (11%) diagnosed with patchy atrophy had optical coherence tomography features of active MFC/PIC lesions, such as focal elevations of the retinal pigment epithelium filled with medium hyperreflectivity material, curvilinear scars (Schlaegel lines), and/or areas of outer retinal atrophy. At the time when the MFC/PIC was diagnosed, the mean age was 57.3 ± 12.0 years, and the mean axial length was 29.2 ± 1.8 mm. Macular neovascularization was found in 45 of eyes (81.8%) with MFC/PIC versus 151 eyes without such findings (33.9%; P0.001). In 25 of the 55 eyes (45.5%), active MFC/PIC lesions were found before the development of the patchy atrophy. The Bruch membrane defects were colocated with these lesions.Active MFC/PIC lesions were identified in a minority of eyes with pathologic myopia, and a subset of these lesions were observed to progress to findings indistinguishable from myopic patchy atrophy. Evidence of MFC/PIC in eyes with pathologic myopia appeared to be a risk factor for the development of macular neovascularization.

Purpose To provide a comprehensive review of rituximab use for the treatment of non-infectious uveitis and scleritis. Methods Review of literature through December 2020. Results Individual data was available for 229 patients with refractory non-infectious uveitis (n = 108) or scleritis (n = 121) who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (uveitis: 67/90, 74.4%; scleritis: 90/96, 93.8%) at a mean of 33.5 months following the diagnosis of uveitis (range = 0 to 168.0 months; median = 24.0 months) and 39.4 months after diagnosis of scleritis (range = 1.0 to 168.0 months; median = 21.0 months). Patients with non-infectious uveitis and scleritis either received prior treatment with corticosteroids only (uveitis: 18/90, 20%; scleritis: 4/94, 4.3%), or with one (uveitis: 19/90, 21.1%; scleritis: 30/94, 31.9%), two (uveitis: 11/90, 12.2%; scleritis 27/94, 28.7%), or three or more (uveitis: 37/90, 41.1%; scleritis: 31/94, 33.0%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (uveitis: 45/87, 51.7%; scleritis: 87/114, 76.3%), followed by the Foster protocol (eight weekly infusions of 375 mg/m2 RTX; uveitis: 18/87, 20.7%; scleritis: 10/114, 8.8%), and the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; uveitis: 5/87, 5.7%; scleritis: 6/114, 5.3%). Various other off-label regimens were used infrequently (uveitis: 19/87, 21.8%; scleritis 11/114, 9.6%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with non-infectious uveitis (81/97, 83.5%). Commonly treated uveitic diagnoses included non-paraneoplastic autoimmune retinopathy (30/107, 28.0%), juvenile idiopathic arthritis (21/107, 19.6%), Vogt-Koyanagi-Harada disease (12/107, 11.2%), and Behçet disease (11/107, 10.3%). Cases of non-infectious scleritis were most commonly attributed to granulomatosis with polyangiitis (75/121, 62.0%) and rheumatoid arthritis (15/121, 12.4%), and showed an even greater rate of positive therapeutic response (112/120, 93.3%) following RTX treatment. No side effects were reported in 76.3% (74/97) of uveitis and 85.5% (71/83) scleritis cases. Of those cases associated with RTX-induced adverse events, the most common were infusion reactions of various severity (11/35, 31.4%). Conclusions Overall, RTX appeared to be both effective and well-tolerated as second or third-line therapy for patients with non-infectious uveitis and scleritis.