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Uveitis is a spectrum of inflammatory disorders characterized by ocular inflammation and is one of the leading causes of preventable visual loss. The main aim of the treatment of uveitis is to control the inflammation, prevent recurrences of the disease and preserve vision while minimizing the adverse effects associated with the therapeutic agents. Initial management of uveitis relies heavily on the use of corticosteroids. However, monotherapy with high-dose corticosteroids is associated with side effects and cannot be maintained long term. Therefore, steroid-sparing agents are needed to decrease the burden of steroid therapy. Currently, the therapeutic approach for non-infectious uveitis (NIU) consists of a step-ladder strategy with the first-line option being corticosteroids in various formulations followed by the use of first-, second- and third-line agents in cases with suboptimal steroid response. Unfortunately, the agents currently at our disposal have limitations such as having a narrow therapeutic window along with their own individual potential side-effect profiles. Therefore, research has been targeted to identify newer drugs as well as new uses for older drugs that target specific pathways in the inflammatory response. Such efforts are made in order to provide targeted and safer therapy with reduced side effects and greater efficacy. Several specially designed molecular antibodies are currently in various phases of investigations that can potentially halt the inflammation in patients with NIU. In the review, we have provided a comprehensive overview of the current and upcoming therapeutic options for patients with NIU.
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Uveítis/tratamiento farmacológico , Alquilantes/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Inflamación/prevención & controlRESUMEN
Purpose: To report 3 cases of retinopathy secondary to ritonavir use in the treatment of HIV. Methods: A retrospective review of patient records was performed for data including ophthalmic examination findings, demographic and HIV clinical characteristics, and progression of maculopathy disease. The review identified 3 patients with a history of HIV treated with antiretroviral therapy including ritonavir who had been evaluated for bilateral vision loss in both eyes. Results: A fundus examination of each patient revealed characteristic macular atrophy, and optical coherence tomography demonstrated corresponding central outer retinal atrophy. Uveitis workup results were unremarkable. Given the characteristics of macular atrophy, history of ritonavir use, and the absence of intraocular inflammation, all 3 patients were diagnosed with bilateral ritonavir-associated retinopathy. Each patients' vision continued to deteriorate, even after the cessation of ritonavir. Conclusions: Ritonavir toxicity should be considered in the differential diagnosis of retinopathy among patients with an exposure history.
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PURPOSE: To evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management. STUDY DESIGN/MATERIALS AND METHODS: Patients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted. RESULTS: A total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 - 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients. CONCLUSION: Our results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.
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Angiografía con Fluoresceína , Uveítis Anterior , Humanos , Angiografía con Fluoresceína/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Uveítis Anterior/diagnóstico , Estudios Retrospectivos , Anciano , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Adulto Joven , Permeabilidad Capilar , Adolescente , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/diagnóstico por imagenRESUMEN
PURPOSE: To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy. OBSERVATIONS: A 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient's history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence. CONCLUSIONS AND IMPORTANCE: Although uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.
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Purpose: To report a case of multifocal central serous chorioretinopathy (CSCR) mimicking Vogt-Koyanagi-Harada (VKH) disease. Methods: A 42-year-old man was evaluated for an exudative retinal detachment (RD) with a presumptive diagnosis of VKH while being treated with corticosteroids. The examination showed subretinal fibrin deposition with a bullous, exudative, macula-involved RD in the left eye and a progressive decline in visual acuity (VA) to hand motions. Multimodal imaging showed multifocal hyperfluorescent leaks bilaterally by angiography, highly suggestive of CSCR exacerbated by corticosteroids. Results: After the multifocal CSCR diagnosis, the systemic corticosteroids were tapered and eventually discontinued. The patient was then managed with focal laser photocoagulation, photodynamic therapy, and acetazolamide. The VA improved to 20/30 with complete resolution of the bullous RD at the 12-month follow-up. Conclusions: Extensive bullous RD with subretinal fibrin deposition is an infrequent manifestation of CSCR commonly associated with corticosteroid use that can mimic VKH. Thus, it is important to distinguish CSCR from VKH and the potential of combination therapy in managing chronic multifocal CSCR with a bullous RD.
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PURPOSE: To report the clinical features and treatment course of a case of central retinal vein occlusion (CRVO) as the initial sign of ocular Bartonella henselae (B. henselae) infection. OBSERVATION: A 36-year-old male was evaluated for unilateral vision loss. He denied prodromal symptoms but reported prior exposure to fleas. Best corrected visual acuity (BCVA) was 20/400 in the left eye. Clinical examination revealed a CRVO with atypical features including significant peripapillary exudates and peripheral vascular sheathing. Laboratory testing revealed elevated B. henselae IgG titers (1:512) with no abnormalities on hypercoagulability testing. The patient was treated with doxycycline and aflibercept with an excellent clinical response and improvement in BCVA to 20/25 in the left eye two months later. CONCLUSION: CRVO is a rare but sight-threatening complication of ocular bartonellosis and can be the presenting sign of infection, even in the absence of cat exposure or prodromal symptoms.
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PURPOSE: To report novel indocyanine green angiography (ICG) findings of optic disc granulomas secondary to sarcoidosis. METHODS: Observational case report. RESULTS: A 36-year-old white male, who had previously been evaluated for birdshot chorioretinopathy and tested HLA-A29 negative, was referred for evaluation of choroidal lesions in both eyes. Fundus examination revealed ovoid choroidal lesions bilaterally in the posterior pole. Optical coherence tomography demonstrated bilateral focal choroidal elevations in the posterior pole and optic discs consistent with granulomas. ICG revealed diffuse choroidal hypocyanescent spots with late-phase focal hypercyanescence of the optic discs in both eyes corresponding to the granulomas. After three months of prednisone and immunomodulatory treatment, the granulomas improved and the optic disc hypercyanescence resolved. CONCLUSION: We describe a case of ocular sarcoidosis mimicking birdshot-like lesions, and ICG findings revealed late hypercyanescence, which resolved with treatment.
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Early diagnosis of infectious uveitis can lead to prompt initiation of treatment to minimize vision-threatening sequelae. As various infectious etiologies of uveitis share similar clinical features, advancements in polymerase chain reaction (PCR) and metagenomic next-generation sequencing (MDS) have shown significant promise in improving diagnostic capabilities. Various techniques of PCR, including real-time, multiplex, comprehensive, and broad-range, have increased the armamentarium for infectious uveitis diagnosis. Additionally, metagenomic deep sequencing technology has provided a methodology to identify causative pathogens as well as novel etiologies of uveitis. This review discusses the diagnostic tools available for infectious uveitis and highlights the advantages and disadvantages of the techniques.
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Methamphetamine use has become a rampant public health issue that not only causes devastating consequences to the user but also poses a burden to surrounding communities. A spectrum of ophthalmic sequelae is associated with methamphetamine use and includes episcleritis, scleritis, corneal ulceration, panophthalmitis, endophthalmitis, retinal vasculitis, and retinopathy. In many instances, prompt recognition of the condition and associated infectious process and early initiation of antimicrobial therapy are crucial steps to preventing vision loss. In this review, we summarize the reported ocular complications that may result from methamphetamine use in addition to several postulated mechanisms regarding the ocular toxicity of methamphetamine. The increasing prevalence of methamphetamine use as a public health threat highlights the need for continued investigation of this ophthalmologic issue.
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PURPOSE: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). CASE REPORT: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. CONCLUSION: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM.
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To report a rare case of a patient with two recurrent episodes of Multiple Evanescent White Dot Syndrome (MEWDS) associated with the second dose and second booster of the mRNA-1273 COVID-19 vaccine (Moderna), and to perform a literature review on COVID-19-vaccine-associated MEWDS. Case Report: A 31-year-old female was evaluated for a temporal scotoma and photopsias that started two weeks after the second dose of the Moderna COVID-19 vaccine. Dilated fundus findings were remarkable for unilateral, small whitish-yellow dots scattered around posterior pole of the left eye, consistent with a diagnosis of MEWDS. The symptoms resolved three months later without treatment. Approximately one year after the first vaccine, the patient received the second Moderna COVID-19 vaccine booster and experienced a recurrence of symptoms with an enlarged scotoma and similar examination findings. The patient was treated with a course of systemic corticosteroids with subsequent clinical improvement. Conclusion: Although uveitis following COVID-19 vaccines is rare, our case highlights a need for increased awareness amongst practitioners regarding COVID-19-vaccine-associated onset or recurrence of ocular inflammatory diseases.
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PURPOSE: To report a case of acute unilateral posterior uveitis as a rare manifestation of giant cell arteritis (GCA). OBSERVATION: A 62-year-old male presented to the clinic for evaluation of decreased vision in the right eye (OD). BCVA in OD was 20/60, and fundus examination revealed 3+ vitreous cells along with several inflammatory precipitates located in posterior vitreous and on surface of retina. Although TAB was inconclusive for GCA, the clinical diagnosis of GCA was made according to the GCA diagnostic criteria. This diagnosis was further supported by 18FDG-PET scan. The patient was started on corticosteroids, and the symptoms improved significantly after first week of treatment. At follow-up visit one month and half later, BCVA improved to 20/40 in the right eye. CONCLUSION: Although GCA is rarely present with uveitis, in case of unilateral posterior uveitis in elderly patient, it should be considered in the differential diagnosis.
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Arteritis de Células Gigantes , Uveítis Posterior , Humanos , Anciano , Persona de Mediana Edad , Arteritis de Células Gigantes/complicaciones , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Uveítis Posterior/diagnóstico , Uveítis Posterior/tratamiento farmacológico , Uveítis Posterior/etiologíaRESUMEN
PURPOSE: To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading. METHODS: In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores. RESULTS: The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+ and 3+ flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P < .05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+ and 1.5/2+ borders of clinical flare, respectively. CONCLUSIONS: LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.
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Rayos Láser , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. METHODS: This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82-C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups. RESULTS: Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). CONCLUSIONS: OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.
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PURPOSE: To correlate the findings of retinal function with multifocal electroretinogram (mfERG), microperimetry (MP), and structural assessments with spectral-domain optical coherence tomography (SD-OCT) in topographically corresponding areas of the macula of patients with birdshot chorioretinopathy (BSCR). METHODS: Patients diagnosed with BSCR by clinical and imaging findings were included in the study. The mfERG was performed using 61 hexagon stimulus patterns grouped into 5 rings (Diagnosys Inc., USA). Individual responses [N1-P1 amplitudes in nanovolt (NV)/degree2 and P1 implicit time in milliseconds (msec)] for each hexagon in the central 3 rings (R1, 0°-2.3°; R2,2.3°-7.7°; and R3, 7.7°-12°) were obtained (19 hexagons). MP examination consisted of Polar 3-12° test with 28 points in 3 concentric rings with diameters of approximately 2.3°, 6.6°, and 11.1° from the foveal center. SD-OCT was performed using macular scans of 20° × 20°. The retinal sensitivity values on MP and thickness values of retinal layers were correlated with the responses on the mfERG for each topographically correlated hexagon. RESULTS: Sixteen eyes of eight patients were included in the study (mean age, 59.87 ± 10.01 years; range, 41-73 years). The amplitudes and the implicit times on mfERG and retinal sensitivities on MP were decreased for each of the 19 hexagons. Considering retinotopically matched points, there was correlation between the retinal sensitivities and mfERG implicit times and response amplitudes in all three rings. The thickness of the retinal pigment epithelium showed modest correlation with the mfERG parameters (ρ = 0.29; p = 0.04). The structural changes on SD-OCT, such as IS-OS disruption, were associated with changes in the mfERG trace arrays. CONCLUSIONS: The structural and functional assessments in retinae of eyes with BSCR suggest that each imaging tool may be capturing unique aspects of retinal dysfunction. Multimodal imaging may allow detailed analyses of retinal damage at various corresponding loci. These findings are important when considering the use of these techniques in BSCR.
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In this study, hydroxyapatite (HAp) coated Mg matrix composites were fabricated for biodegradable implant applications. Spark plasma sintering was employed to fabricate the Mg-10 wt% ZnO composite substrates. HAp was coated on the surface of the sintered composites and pure Mg by a chemical solution treatment. SEM and optical micrographs of coated samples showed that HAp grew homogeneously and formed a layer on the entire surface of both pure sintered Mg and Mg composites. The immersion and polarization test results demonstrated that the HAp coating significantly improved the corrosion resistance of the sintered composites. While the HAp coating layer is not effective in the improvement of the pure Mg substrate, cell culture test results revealed that the HAp coating improved cell adhesion and proliferation on the composites effectively through 72 h, while no cell could survive on the uncoated composites after 72 h. In addition, the corrosion tests and cell culture test results indicated that the composite with longer sintering time has better corrosion resistance and cell viability than those of the composite with shorter sintering time. The findings suggested that the HAp-coated Mg-10 wt% ZnO-2.5 h + 10 min composite is a high-potential candidate for biodegradable implant applications.
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BACKGROUND: Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis. MAIN BODY: Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor. CONCLUSION: Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.
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PURPOSE: The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis® (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC). METHODS: In this prospective study, FAF was performed using BL (λ = 488 nm) and GL (λ = 532 nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately. RESULTS: One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5 ± 0.88, 1.23 ± 0.58, and 4.73 ± 2.85, respectively) and for GAF were (0.78 ± 0.20, 0.78 ± 0.20, and 1.62 ± 0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68 ± 1.02, 1.66 ± 1.15, and 7.75 ± 6.82, respectively) and for GAF were (0.95 ± 0.59, 0.79 ± 0.45, and 2.50 ± 1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p < 0.001). The strength of the correlation (r) between ratios for BAF and GAF was weak or not statistically significant in both normal and RC subjects (p > 0.05). CONCLUSION: The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.