Interobserver Reliability and Sensitivity to Change of a Composite Ocular Inflammatory Activity Index: UVEDAI©.

INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis.

INTRODUCTION: Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. METHODS: A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. RESULTS: Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate-high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild-moderate. CONCLUSIONS: The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.

Outcome Measures for Disease Monitoring in Intraocular Inflammatory and Infectious Diseases (OCTOMERIA): Understanding the Choroid in Uveitis with Optical Coherence Tomography (OCT).

PURPOSE: To compare imaging modalities for the choroid of the eye, and evaluate various choroidal changes in uveitides entities. METHODS: A comprehensive systematic literature review was conducted looking at current imaging modalities available to assess choroid architecture and commonly used parameters available to qualify and quantify choroidal changes, before looking at specific uveitides entities with choroidal involvement which have been broadly separated into non-infectious and infectious in etiology. RESULTS: We describe the various modalities currently available to evaluate the choroid of the eye such as Ultrasound B Scan, ICGA, and OCT. Choroidal changes in various ocular and systemic diseases such as Behcet's Disease, Sarcoidosis, Syphillis, Tuberculosis, and many more have been reported and published. CONCLUSION: Multiple choroidal tomographic and angiotomographic findings have been demonstrated for evaluation in uveitis. These findings can manifest in multiple ocular and systemic diseases, and can be illustrated using the various imaging modalities at present. Future advancements in choroidal imaging would help to adapt these findings into parameters for clinical practice to properly evaluate these ocular and systemic diseases.

CHARACTERIZING COVID-19-RELATED RETINAL VASCULAR OCCLUSIONS: A Case Series and Review of the Literature.

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Vitreous and Optic Nerve Infiltration of an Adrenal B Lymphoma.

AIM: This study aimed to report a case of vitreous and optic nerve infiltration of a primary adrenal B lymphoma. CASE REPORT: An 81-year-old patient consulted for decrease in vision in the left eye and pain with ocular movements during the last week. The patient was being treated with chemotherapy for an adrenal gland diffuse large B-cell lymphoma. On examination, vitritis was seen in both eyes and optic disc edema in his left eye. After an extensive study based on orbital and brain magnetic resonance imaging and vitreous cytology, an ocular infiltration by systemic B lymphoma was confirmed. A treatment based on intravitreal methotrexate was carried out, achieving the regression of the vitreous infiltration and resolution of the optic disc edema. Systemic B lymphoma metastasizing ocular structures is extremely infrequent. The manifestations may mimic an inflammatory disease. Ophthalmologists should be aware of these manifestations and consider among the masquerade syndromes.

Fluocinolone Implant for Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis Syndrome: A Case Report.

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare and progressive disorder that predominantly affects both the eyes of young female individuals and can threaten visual function. Peripheral ischemia and macular exudation are common findings in patients. The treatment options include panretinal photocoagulation (PRP), systemic immunosuppression, and intravitreal antiangiogenic and corticosteroid therapy. Fluocinolone acetonide intravitreal implant is approved for the treatment of nonanterior noninfectious uveitis and diabetic macular edema (ME), with an estimated therapeutic duration of 3 years. We describe a case of IRVAN syndrome in a child with ME who had been previously treated with PRP, antiangiogenic therapy, and several dexamethasone intravitreal implants and received a fluocinolone acetonide intravitreal implant in her right eye. The patient showed stabilization of the visual acuity and a marked reduction of the macular thickness 1 month after the treatment. At 12-month follow-up, the patient required perifoveal focal photocoagulation due to a rebound of the ME. After 2 years of follow-up, visual acuity remains stable and macular retinal thickening under control. Local long-standing steroid therapy has proved to be quite efficient in controlling the progression of the disease in our patient.

Adalimumab in Elderly Patients with Non-Infectious Uveitis. Safety and Efficacy.

Purpose: To assess the efficacy and safety of adalimumab in elderly patients with noninfectious uveitis (NIU).Methods: An observational, retrospective, multicenter study was done. Changes in best-corrected visual acuity (BCVA), inflammatory activity parameters, central retinal thickness (CRT), and the occurrence of adverse events (AE) developed during follow-up were recorded.Results: A total of 82 eyes from 41 patients 60 years of age and older with noninfectious uveitis treated with adalimumab were included. A significant improvement in BCVA (71.5 to 75.4 letters, p = .001) and in CRT (311.1 µm to 265 µm, p = .001) was observed. Moreover, a significant decrease from baseline in the rate of patients with anterior chamber cell (ACC) >0+ (34.6% to 5.7%, p = <0.001) or vitreous haze>0+ (21.3% to 4.3%, p = .002) was determined. AEs were observed in 11 patients (26.8%).Conclusion: Adalimumab can be safe and efficacious for the treatment of NIU in patients 60 years of age and older.

Paraneoplastic Focal Outer Retinitis and Optic Neuropathy in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5, Anti-HU and Anti-Amphiphysin Antibodies.

Our aim is to describe clinical and optical coherence tomographic features of acute paraneoplastic focal outer retinitis associated with optic neuropathy in a patient diagnosed with small cell lung carcinoma. Bilateral focal outer retinitis, bilateral optic disc oedema and vitritis were identified in a patient with progressive bilateral visual loss and ataxia. Spectral domain optical coherence tomography (SD-OCT) revealed various extents of granular hyperreflectivity and atrophy of the macular outer retinal layers. Serum and cerebrospinal fluid positivity for anti-CRMP5, anti-HU and anti-amphiphysin antibodies intensified the search for an underlying malignancy, and a small cell lung carcinoma (SCLC) was finally diagnosed. Local and oral steroids along with systemic chemotherapy and radiotherapy achieved cancer remission and partial recovery from the ophthalmic manifestations. Focal outer retinitis associated with optic disc oedema and antibody positivity facilitated the diagnosis of SCLC in a localized stage. SD-OCT allowed the characterization of this entity, expanding the spectrum of paraneoplastic ophthalmological syndromes.

Systemic Regulatory T Cells and IL-6 as Prognostic Factors for Anatomical Improvement of Uveitic Macular Edema.

Purpose: To investigate whether systemic immune mediators and circulating regulatory T cells (Tregs) could be prognostic factors for anatomic outcomes in macular edema secondary to non-infectious uveitis (UME). Methods: Multicenter, prospective, observational, 12-month follow-up study of 60 patients with UME. Macular edema was defined as central subfield thickness (CST) > 300 µm measured with spectral domain optical coherence tomography (SD-OCT). Serum samples and peripheral blood mononuclear cells (PBMC) were obtained from venous blood extraction at baseline. Serum levels of IL-1ß, IL-6, IL-8, IL-17, MCP-1, TNF-α, IL-10, and VEGF were determined by Luminex. Tregs population, defined as CD3+CD4+FoxP3+ in PBMC, was determined by flow cytometry. Main outcome measure was the predictive association between searched mediators and CST sustained improvement, defined as CST < 300 microns or a 20% CST decrease, at 6 months maintained until 12-months compared to baseline levels. Results: Multivariate logistic regression analysis showed an association between CST sustained improvement at 12 months follow-up and IL-6 and Tregs baseline levels. Higher IL-6 levels were associated with less events of UME improvement (OR: 0.67, 95% CI (0.45-1.00), P = 0.042), whereas higher levels of Tregs favored such improvement (OR: 1.25, 95% CI: 1.12-2.56, P = 0.049). Conclusions: Increased levels of Tregs and reduced levels of IL-6 in serum may be prognostic factors of sustained anatomical improvement in UME. These findings could enforce the opportunity to develop more efficient and personalized therapeutic approaches to improve long-term visual prognosis in patients with UME.

Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis.

AIMS: We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. MATERIAL AND METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of >300 µm as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm2 area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or <300 µm) within a 12 month period. RESULTS: Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. CONCLUSION: Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.

Behavior of hyperreflective foci in non-infectious uveitic macular edema, a 12-month follow-up prospective study.

BACKGROUND: Hyperreflective foci have been described in OCT imaging of patients with retinal vascular diseases. It has been suggested that they may play a role as a prognostic factor of visual outcomes in these diseases. The purpose of this study is to describe the presence of hyperreflective foci in patients with non-infectious uveitic macular edema and evaluate their behavior after treatment. METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Inclusion criteria were age > 18 years and a diagnosis of non-infectious uveitic macular edema, defined as central macular thickness of > 300 µm as measured by OCT and fluid in the macula. Collected data included best corrected visual acuity, central macular thickness and the presence, number and distribution (inner or outer retinal layers) of hyperreflective foci. Evaluations were performed at baseline, and at 1, 3, 6, and 12 months after starting treatment. RESULTS: We included 24 eyes of 24 patients. The frequency of patients with ≥11 hyperreflective foci was 58.4% at baseline, falling to 20.8% at 12 months. Further, hyperreflective foci were observed in the outer retinal layers in 50% of patients at baseline and just 28.6% at 12 months. Mean LogMAR visual acuity improved from 0.55 (95% CI 0.4-0.71) at baseline to 0.22 (95% CI 0.08-0.35) at 12 months (p < 0.001). Mean central macular thickness decreased from 453.83 µm (95% CI 396.6-511) at baseline to 269.32 µm (95% CI 227.7-310.9) at 12 months (P < 0.001). Central macular thickness was associated with number (p = 0.017) and distribution (p = 0.004) of hyperreflective foci. CONCLUSIONS: We have observed hyperreflective foci in most of our patients with non-infectious uveitic macular edema. During follow-up and after treatment, the number of foci diminished and they tended to be located in the inner layers of the retina.

Dexamethasone intravitreal implants in the management of tubercular multifocal serpiginoid choroiditis.

BACKGROUND: Continuous progression of lesions despite an adequate treatment has been described in tubercular multifocal serpiginoid choroiditis. Reported treatments for this paradoxical response include systemic steroids, immunosuppressive drugs, and intravitreal methotrexate. We describe the use of dexamethasone intravitreal implants in a patient presenting with this condition. FINDINGS: A 46-year-old woman sought medical attention for scotomas in her left eye. Tests suggested multifocal serpiginoid choroiditis associated with latent tuberculosis infection, and hence, she was started on anti-tuberculosis drugs in combination with corticosteroids. Given that lesions progressed despite this treatment, we began treatment with dexamethasone intravitreal implants. After injection of the second implant, we succeeded in inactivating the inflammatory process. CONCLUSIONS: Dexamethasone intravitreal implants may be a suitable alternative to systemic steroids or immunosuppressive therapy in the management of continuous progression of lesions in tubercular multifocal serpiginoid choroiditis.

SAFETY AND EFFICACY OF INTRAVITREAL DEXAMETHASONE IMPLANTS IN THE MANAGEMENT OF MACULAR EDEMA SECONDARY TO INFECTIOUS UVEITIS.

PURPOSE: To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. METHODS: We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. RESULTS: We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 µm (115) at baseline and 266.3 µm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. CONCLUSION: In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients.

Clinical Manifestations and Outcomes of Syphilis-associated Uveitis in Northern Spain.

PURPOSE: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain. METHODS: Retrospective review of clinical records in eight general uveitis referral centers. RESULTS: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20-20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009). CONCLUSIONS: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good.

Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: indications, outcomes, and reinjection frequency.

PURPOSE: To identify clinical outcomes and treatment patterns of intravitreal dexamethasone implant (Ozurdex; Allergan, Inc) in noninfectious uveitis in the clinical setting. DESIGN: Multicenter retrospective cohort study. METHODS: Eighty-two eyes (63 patients) receiving 142 implant injections over 35 months were included. Treatment indication, uveitis diagnosis, visual acuity, intraocular pressure, vitreous haze score, central retinal thickness by optical coherence tomography, phakic status, number of injections, time to reinjection, systemic treatments, and complications data were collected. Time to visual acuity and vitreous haze score improvement as per the Standardization of Uveitis Nomenclature guidelines were also determined. RESULTS: The probability of visual acuity improvement (≥0.3 logarithm of the minimal angle of resolution units improvement) was 39% at 1 month, 49% at 3 months, 52% at 6 months, and 58% at 12 months. Eyes with baseline vitritis (vitreous haze score ≥+0.5, n = 45) had a probability of vitreous haze score improvement (2-step decrease or change from +0.5 to 0) at 2 weeks of 41%, at 1 month 63%, at 3 months 73%, at 6 months 79%, and at 12 months 88%. In eyes that completed 12-month follow-up (n = 54), 40.7% underwent 2 injections (mean time to second injection of 6.6 ± 1.9 months) and 11.2% required ≥3 injections (mean time to third injection of 11 ± 1.5 months). CONCLUSIONS: Dexamethasone implant use in uveitis provides favorable visual acuity and vitreous haze score outcomes but requires repeated injections, an important consideration when choosing intraocular treatment as a route to controlling uveitis.