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Radiology and Oncology Apr 2022Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1... (Review)
Review
BACKGROUND
Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases.
PATIENTS AND METHODS
A literature review using PubMed search was conducted to identify cases of uveitis secondary to durvalumab and cases of uveitis with optic disc oedema secondary to ICI use that were reported prior to November 14, 2021. Additionally, we report two cases of uveitis consequent on durvalumab treatment.
RESULTS
Five cases of uveitis secondary to durvalumab use were identified in the literature. Anterior, posterior uveitis and vasculitis were reported. Additionally, we present a case of bilateral intermediate uveitis with bilateral optic disc oedema and a case of bilateral posterior uveitis. Our further search revealed 12 cases of uveitis with optic disc oedema secondary to ICI use, with the majority of cases reported secondary to PD-1 inhibitors.
CONCLUSIONS
Rarely reported, uveitis secondary to durvalumab can present various clinical pictures and requires a thorough diagnostic workup. Once the diagnosis is established, treatment, commonly with a local or systemic corticosteroid, should be adapted to the severity of the inflammation.
Topics: Antibodies, Monoclonal; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Papilledema; Uveitis; Uveitis, Posterior
PubMed: 35412706
DOI: 10.2478/raon-2022-0007 -
Ophthalmology Dec 2018In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has... (Review)
Review
In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 μg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 μg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-μg group than in the 44-μg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 μg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Immunosuppressive Agents; Intravitreal Injections; Panuveitis; Sirolimus; Uveitis, Intermediate; Uveitis, Posterior
PubMed: 30060978
DOI: 10.1016/j.ophtha.2018.06.015 -
The British Journal of Ophthalmology Sep 1974
Topics: Adult; Antitubercular Agents; Azathioprine; Choroiditis; Cicatrix; Cytarabine; Female; Fluorescein Angiography; Fundus Oculi; Humans; Macula Lutea; Male; Prednisone; Retinal Vessels; Skin Tests; Tuberculosis, Pulmonary; Visual Acuity
PubMed: 4433491
DOI: 10.1136/bjo.58.9.777 -
Diagnostics (Basel, Switzerland) Sep 2022Optical coherence tomography angiography (OCT-A) has been applied to uveitis and intraocular inflammation since its availability after 2014. The imaging of retinal and...
PURPOSE
Optical coherence tomography angiography (OCT-A) has been applied to uveitis and intraocular inflammation since its availability after 2014. The imaging of retinal and choroidal vascularization without the use of dyes was a major development and represented a potentially valuable tool in ocular research. In addition to such use, OCT-A is often put forward as being able to potentially replace invasive methods needing dye injection, such as fluorescein angiography (FA) and indocyanine green angiography (ICGA). The aim of this review was to establish whether OCT-A was sufficiently useful in everyday routine clinical practice to monitor disease evolution and to perform treatment adjustments to the extent that it could reliably replace the standard dye methods.
METHODS
Selective literature review and analysis of own data and experience.
RESULTS
OCT-A is a technologically high-grade imaging modality allowing to analyze retinal circulation in inflammatory diseases of the posterior pole with a high sensitivity useful for research purposes. However, there is no evidence that it reaches equal effectiveness in the routine management of posterior uveitis involving the retina. OCT-A is unable to show leakage. In choriocapillaritis involving pre-capillary vessels, it shows capillary drop-out but does not seem to have an advantage over ICGA except that it can be repeated easily, not being invasive, and so allows a closer follow-up. It is, however, less useful in end-choriocapillary non-perfusion, such as in MEWDS. For choroidal stromal inflammation, OCT-A is ill-suited as it only shows inconsistent secondary circulatory changes produced by choroidal foci. OCT-A seems to be useful in the diagnosis and follow-up of inflammatory chorioneovascularisation (iCNV), although dye exams are more precise in showing the activity of the iCNV.
CONCLUSION
In summary, OCT-A is a very sensitive modality for the retinal circulation in uveitis for research purposes; it is sometimes useful for close follow of choriocapillary drop-out but not in end-capillary non-perfusion. Its use for monitoring purposes in stromal choroiditis, however, is questionable. Its claim to possibly replace classical angiographic work-up for the practical management of posterior uveitis is largely overrated.
PubMed: 36292075
DOI: 10.3390/diagnostics12102384 -
Clinical Ophthalmology (Auckland, N.Z.) 2023The present study aimed to assess the efficacy and safety associated to the treatment of patients with non-infectious posterior uveitis with intravitreal dexamethasone...
PURPOSE
The present study aimed to assess the efficacy and safety associated to the treatment of patients with non-infectious posterior uveitis with intravitreal dexamethasone (DEX) implants in a real-world clinical setting.
PATIENTS AND METHODS
This is a retrospective, single center analysis of the data from 29 patients with non-infectious posterior uveitis in whom 38 eyes were treated with dexamethasone intravitreal implants in routine clinical practice between January 2012 and October 2017. The parameters of visual acuity (VA), intraocular pressure (IOP) and central retinal thickness (CRT) were recorded 6 weeks after the first implant was administered, in accordance with the clinical guidelines for the use of these implants, and after a 6-month follow-up period. In addition, the formation of cataracts was evaluated at 12 months.
RESULTS
Treatment with the DEX implant caused a significant improvement in the VA from baseline at 6 weeks in eyes treated with 2-6 implants and for eyes without cataracts. A significant decrease in CRT was observed relative to the baseline at 6 weeks for eyes treated with 1 and 2-6 implants, which was maintained at 6 months for those eyes treated with 2-6 implants. This significant improvement in CRT at 6 weeks and 6 months was evident in eyes with and without cataracts. During the study period, the IOP was found to increase significantly from baseline at 6 weeks in some eyes but this was managed topically, and no surgical intervention was necessary.
CONCLUSION
Intravitreal DEX implants represent an effective and safe therapy for the treatment of non-infectious uveitis in routine clinical practice, producing favorable visual and anatomical outcomes after the administration of just 2-6 DEX implants.
PubMed: 36814784
DOI: 10.2147/OPTH.S393662 -
Clinical & Experimental Ophthalmology 2013The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this... (Review)
Review
The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.
Topics: Animals; Antiprotozoal Agents; Chorioretinitis; Drug Therapy, Combination; Glucocorticoids; Humans; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Ocular
PubMed: 22712598
DOI: 10.1111/j.1442-9071.2012.02838.x -
Journal of Ocular Pharmacology and... May 2015This study aims at the development and preliminary evaluation of dexamethasone nanomicelles for treating posterior uveitis. Nanomicelles were formulated using polyoxyl...
PURPOSE
This study aims at the development and preliminary evaluation of dexamethasone nanomicelles for treating posterior uveitis. Nanomicelles were formulated using polyoxyl 40 stearate (P40S) and polysorbate 80 (P80), which are approved by the FDA for ocular use.
METHODS
Dexamethasone nanomicelles were prepared and characterized for critical micellar concentration, solubility of dexamethasone, particle size, surface charge, morphology, in vitro drug release, clarity, stability, filtration efficiency, and sterility. Ocular tolerance and the tissue drug distribution of dexamethasone were assessed in rabbits after single and multiple topical administration.
RESULTS
Dexamethasone nanomicelles (0.1% w/v) were successfully developed and characterized with an optimized composition of P40S/P80=7/3 by weight. The mean diameter of blank and drug-loaded nanomicelles was 13.3±0.4 and 14.5±0.4 nm, respectively. Transmission electron microscopy images revealed the spherical structure of nanomicelles. Nanomicelles were found to be stable with respect to clarity, size and drug content at 4°C and 25°C for up to 6 months. No irritation or redness was observed in the treated eyes as compared with the untreated control rabbit eyes. Therapeutic concentrations of dexamethasone were observed in the retina and choroid after single and multiple topical application in rabbits.
CONCLUSION
In conclusion, the nanomicelles of P40S and P80 could efficiently solubilize 0.1% dexamethasone in their cores. The results also indicate that mixed nanomicelles could be utilized as a potential delivery system for delivering dexamethasone to treat the back of the eye diseases such as posterior uveitis after topical application.
Topics: Administration, Ophthalmic; Animals; Calorimetry, Differential Scanning; Dexamethasone; Drug Delivery Systems; Glucocorticoids; Male; Micelles; Microscopy, Electron, Transmission; Nanoparticles; Rabbits; Solubility; Uveitis, Posterior
PubMed: 25839185
DOI: 10.1089/jop.2014.0152 -
BMC Ophthalmology Apr 2022Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or... (Observational Study)
Observational Study
BACKGROUND
Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported.
METHODS
An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively.
RESULTS
Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14-85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation.
CONCLUSION
Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cataract; Female; Humans; Inflammation; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Uveitis; Uveitis, Posterior; Vitrectomy; Young Adult
PubMed: 35439966
DOI: 10.1186/s12886-022-02405-y -
Arquivos Brasileiros de Oftalmologia 2022The aim of this study was to describe the epidemiological profile of uveitis cases treated at University Hospital Clementino Fraga Filho and to identify the presentation...
PURPOSE
The aim of this study was to describe the epidemiological profile of uveitis cases treated at University Hospital Clementino Fraga Filho and to identify the presentation pattern of intraocular inflammation on the basis of clinical, anatomical, etiological, and demographic criteria.
METHODS
A retrospective study was conducted using data from the medical records of 408 patients with active disease who attended the ophthalmology service between March and October 2018. Age, sex, visual acuity at the time of diagnosis, anatomical and etiological diagnoses, the clinical aspect, and the main symptoms reported during anamnesis were described.
RESULTS
Of the 408 patients in the study, 52% were male and 48% were female. The patients' mean age was 42 years, and most (84%) were between 19 and 64 years old. Anterior uveitis was observed in 37.75% of the patients; posterior uveitis, in 49.75%; panuveitis, in 4.66%; and intermediate uveitis, in 3.43%. Only 18 patients (4.41%) presented with scleritis. Of the 390 patients with anatomical classifications, 76% had known etiologies, with the most prevalent diagnoses being toxoplasmosis (35.4%), followed by juvenile idiopathic arthritis (6.4%), ankylosing spondylitis (5.9%), and syphilis (4.9%). Infectious uveitis corresponded to 49.7% of the patients, while 26.6% of the cases were of noninfectious origin. Anterior uveitis had the highest number of cases classified as idiopathic (49.4%). In the cases of posterior uveitis, the etiology was established 94% of the time. The most frequent symptoms were ocular pain (71.8%) and blurring vision (56.8%).
CONCLUSIONS
The present study confirmed the historical importance of infectious uveitis in our population, especially ocular toxoplasmosis. Uveitis appears to have no predilection for sex but mainly affects young people of working age, thus generating social and economic consequences. Despite the evolution of diagnostic methods, idiopathic uveitis remains one of the major etiologies. Epidemiological studies point to different presentation patterns of uveitis in different populations, but these may reflect the distinct characteristics of each institution.
Topics: Adolescent; Adult; Brazil; Female; Hospitals, University; Humans; Male; Retrospective Studies; Uveitis; Uveitis, Anterior; Uveitis, Posterior; Vision Disorders
PubMed: 34586241
DOI: 10.5935/0004-2749.20220040 -
Molecular Vision 2012To investigate the associations of complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) gene polymorphisms in patients with non-infectious intermediate and...
OBJECTIVE
To investigate the associations of complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) gene polymorphisms in patients with non-infectious intermediate and posterior uveitis.
METHODS
The study cohort consisted of a total of 95 Chinese non-infectious uveitis patients, including 38 patients with intermediate uveitis (IU), 38 patients with Vogt-Koyanagi-Harada disease (VKH), and 19 patients with Behçet's disease and 308 healthy controls. The genotypes of CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were determined using TaqMan single nucleotide polymorphism genotyping assays.
RESULTS
The frequency of carriers of G allele for CFH-rs800292 was significantly higher in patients with non-infectious intermediate and posterior uveitis than in controls (GG/AG versus AA; p=0.02). No significant association was found between uveitis and both KIAA1109-rs4505848 and IL27-rs4788084. In stratified analysis by gender, the frequency of carriers with G allele for KIAA1109-rs4505848 was significantly higher in male uveitis patients than in male controls (GG/AG versus AA; p=0.034). There was no significant difference in allelic and genotypic frequencies for CFH-rs800292 and IL27-rs4788084 in either male or female groups. In addition, higher frequency of KIAA1109-rs4505848 G allele was found in Behçet's disease patients compared with controls and IU patients (p=0.01 and p=0.003, respectively).
CONCLUSIONS
Our results demonstrated that CFH-rs800292 and KIAA1109-rs4505848 are associated with non-infectious intermediate and posterior uveitis. Moreover, gender susceptibility for uveitis might be involved in the KIAA1109 gene and the KIAA1109-rs4505848 polymorphism might be associated with the development of Behçet's disease.
Topics: Adolescent; Adult; Aged; Alleles; Asian People; Case-Control Studies; Complement Factor H; Female; Gene Frequency; Genotype; Humans; Interleukins; Male; Middle Aged; Polymorphism, Single Nucleotide; Uveitis, Anterior; Uveitis, Posterior; Uveomeningoencephalitic Syndrome
PubMed: 22876110
DOI: No ID Found