The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Epidemiology of Pediatric Uveitis in Argentina.

PURPOSE: To explore the geographic variability of the epidemiology of pediatric uveitis, which, although rare in children, carries a significant risk of morbidity. METHODS: This was a retrospective review conducted at two tertiary referral centers in Buenos Aires, Argentina. Demographic and clinical data of patients younger than 16 years diagnosed as having uveitis between January 1, 2006 and October 1, 2014 were collected. RESULTS: A total of 257 patients (380 eyes) were included in the study. Cases tended to be unilateral (134, 52.1%), granulomatous (146, 56.8%), and localized to the posterior segment (121, 47.1%). Toxoplasmosis was the most common etiology (98, 38.1%). DISCUSSION: The spectrum of pediatric uveitis in Buenos Aires most closely resembles that of Colombia. Understanding these geographic variations is important to aid providers who are caring for children in an increasingly globalized world. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis.

BACKGROUND: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide. METHODS AND FINDINGS: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836). RESULTS: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%-58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%-48%) and blindness in 20% (95% CI 13%-30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72-8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59-6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment. CONCLUSION: Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.

Correlation between Subfoveal Choroidal Thickness and Anterior Segment Inflammation in Patients with Chronic Stage of Vogt-Koyanagi-Harada Disease.

PURPOSE: To correlate changes in subfoveal choroidal thickness (SCT) with the degree of anterior inflammatory activity in chronic Vogt-Koyanagi-Harada (VKH) disease. METHODS: Anterior segment inflammation was assessed using SUN anterior chamber cell grading criteria, and SCT was measured using EDI-OCT in patients with VKH at multiple visits. ANOVA was used to compare the mean SCT for each anterior chamber cell grade. Regression analysis was used to correlate the anterior segment cell grade and the SCT. RESULTS: 14 patients were included in the study. A total of 432 data points consisting of SCT and anterior segment cell values were analyzed. ANOVA demonstrated significant difference between the mean SCT for different anterior chamber cell grades (p < .0001). Regression analysis demonstrated significant correlation between SCT and grade of anterior chamber cells (R2 = 0.37, p < .001). CONCLUSIONS: Chronic VKH is characterized by a dynamic change in SCT that correlates with anterior segment inflammatory activity.

New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review.

BACKGROUND: Non-infectious uveitis (NIU) is an immune-mediated disease with clinical symptoms such as eye pain, redness, floaters, and light sensitivity. NIU is one of the leading causes of preventable blindness. OBJECTIVE: This review describes current and emerging therapies for NIU. METHODS: PubMed searches were conducted using the terms uveitis, therapy, corticosteroids, immunomodulators, biologics, intravitreal injections, intraocular implants, and adverse events deemed relevant if they presented data relating to prevalence, diagnosis, and treatment of uveitis. RESULTS: Diagnosis and management of NIU may require collaboration among different healthcare providers, including ophthalmologists and rheumatologists. Although many patients with NIU respond to corticosteroid (CS) therapy, long-term CS use can be associated with potentially severe adverse events. Localized CS therapies have been developed to reduce adverse events; however, some intravitreal injections and intraocular implants were linked to elevated intraocular pressure and cataracts. CS-sparing therapies such as biologics have demonstrated efficacy and safety while reducing CS burden. Biologics targeting tumor necrosis factor provide CS-sparing options for patients with NIU. Additional studies are needed to address long-term efficacy and safety of biologics targeting IL-6 and inhibitors of JAK/STAT. CONCLUSION: Biologics, JAK/STAT inhibitors, and improved localized therapies may provide additional options for patients with NIU.

Spectral optical coherence tomography findings in an adult patient with syphilitic bilateral posterior uveitis and unilateral punctate inner retinitis.

PURPOSE: To describe the spectral domain optical coherence tomography (SD-OCT) features of a punctate inner retinitis, a rare ocular manifestation of syphilis, in an HIV positive adult patient. OBSERVATIONS: In the right eye, SD-OCT images during the active period showed hyperreflectivity of the full thickness of the inner retina, precluding the individualization of the layers. In addition, multifocal areas with higher hyperreflectivity were identified within the affected retina. Once the lesion became inactive, SD-OCT images revealed inner retina layers atrophy, disruption of the ellipsoid layer, and multifocal damage to the retinal pigment epithelium layer. CONCLUSION AND IMPORTANCE: Punctate inner retinitis affects the full thickness retina, leading to severe retinal damage, along with multifocal damage of the retinal pigment epithelium. The multifocal white retinal lesions observed within the affected retinal area correlated with the presence of intense hyperreflective dots within the retina showed by SD-OCT. These lesions are deeper than was described in other reports.

Twenty-Four Months Follow-Up of Intravitreal Bevacizumab Injection Versus Intravitreal Triamcinolone Acetonide Injection for the Management of Persistent Non-Infectious Uveitic Cystoid Macular Edema.

PURPOSE: To report the efficacy of intravitreal bevacizumab (IVB) injection versus intravitreal triamcinolone acetonide (IVT) for persistent non-infectious uveitic cystoid macular edema (CME). METHODS: Interventional retrospective comparative case series evaluated 37 consecutive patients (44 eyes) with completely controlled uveitis and recalcitrant CME. Patients received repeated injections of 1.25 mg of IVB or 4 mg of IVT. RESULTS: Best-corrected visual acuity (BCVA) at baseline and 24 months was logMAR 1 and 0.8 respectively, in the IVB group (p = 0.002) and; logMAR of 1.1 and 0.6, in the IVT group (p = 0.001). Central macular thickness at baseline and 24 months was 399.2 µm and 333.7 µm (p < 0.0009), respectively, for the IVB group and; 464.4 µm and 316.5 µm in the IVT group (p = 0.044). Postoperatively, IOP increased in the IVT group. CONCLUSIONS: Repeated injections with IVT improve BCVA as effectively as repeated injections with IVB in the long-term management of persistent uveitic CME.

Bilateral Acute Retinal Necrosis: Clinical Features and Outcomes in a Multicenter Study.

Purpose: To describe clinical features and outcome in bilateral acute retinal necrosis (BARN). Methods: Observational retrospective longitudinal review of ocular findings. Results: Thirty eyes of 15 patients (age 44.1 ± 15.8). Delay of involvement between eyes was 57.2 ± 105.2 months (median 3, range 0.5-360). Herpes simplex virus (HSV)-1 was the most frequent (20 eyes, 66.6%), followed by HSV-2 (five eyes, 16.7%) and varicella zoster virus (VZV, four eyes, 13.3%). Visual acuity worsened in 7 (23%) eyes, improved in 4 (13%), and remained stable in 19 (63%). Major complications included retinal detachment (11 eyes, 36%), optic atrophy (11 eyes, 33%), proliferative vitreoretinopathy (four eyes, 13.3%), neovascular glaucoma (four eyes, 13.3%), phthisis bulbi (three eyes, 10%). Symptoms-to-referral average time was 2.7 ± 1.0 weeks (range 1-4). Conclusions: In our study BARN was associated with severe visual outcome and high rate of ocular complications. Although BARN is a rare disease, the course is aggressive, regardless prompt referral in tertiary-care uveitis centers.

Immune Mediators against Toxoplasma Gondii during Reactivation of Toxoplasmic Retinochoroiditis.

Purpose: The purpose of this article is to analyze possible associations between systemic and ocular cytokine levels and specific clinical ophthalmologic signs from patients with a reactivation of toxoplasmic retinochoroiditis (RTR). Methods: A total of 18 patients with an active RTR episode, 8 patients with inactive scars, and 14 control patients were included in the study. Serum samples and aqueous humor (AH) samples were analyzed for IFN (interferon)-γ, interleukin (IL)-10, and IL-6 levels by ELISA. Inflammation grade, location, and size of the retinochoroidal active lesion, sampling time, and time to resolution were recorded. Results: A significantly negative correlation between AH and serum levels of IFN-γ was detected (p < 0.05). Patients with an AH IFN-γ/IL-10 ratio lower than 1 were associated with the longest time to resolution and/or severe complications. Conclusion: Serum IFN-γ levels may be used as a prognostic marker for both time to resolution and the development of possible severe complications during a given RTR episode.

Catching the therapeutic window of opportunity in early initial-onset Vogt-Koyanagi-Harada uveitis can cure the disease.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune granulomatous choroiditis that begins in the choroidal stroma. The aim of this review was to gather a body of evidence for the concept of a window of therapeutic opportunity, defined as a time interval following initial-onset disease during which adequate treatment will substantially modify the disease outcome and possibly even lead to cure, similar to what has been described for rheumatoid arthritis. METHODS: We reviewed the literature and consulted leading experts in VKH disease to determine the consensus for the notion of a therapeutic window of opportunity in VKH disease. RESULTS: We found a substantial body of evidence in the literature that a therapeutic window of opportunity exists for initial-onset acute uveitis associated with VKH disease. The disease outcome can be substantially improved if dual systemic steroidal and non-steroidal immunosuppressants are given within 2-3 weeks of the onset of initial VKH disease, avoiding evolution to chronic disease and development of "sunset glow fundus." Several studies additionally report series in which the disease could be cured, using such an approach. CONCLUSIONS: There is substantial evidence for a therapeutic window of opportunity in initial-onset acute VKH disease. Timely and adequate treatment led to substantial improvement of disease outcome and prevented chronic evolution and "sunset glow fundus," and very early treatment led to the cure after discontinuation of therapy in several series, likely due to the fact that the choroid is the sole origin of inflammation in VKH disease.

Regional Differences in the Clinical Manifestation of Ocular Toxoplasmosis Between the Center and Northeast of Argentina.

Purpose: To compare the clinical characteristics of patients with active episodes of ocular toxoplasmosis from three provinces, Misiones, Santa Fe, and Buenos Aires, Argentina. Methods: Patients with a diagnosis of ocular toxoplasmosis from three databases of four tertiary referral uveitis centers were reviewed. Collected data included presentation of the retinochoroiditis, location of the active lesions, associated inflammatory ocular signs and complications. Results: Three hundred thirty-four patients were included in this study. Bilateral involvement of the ocular disease occurred in 26 patients in Misiones (35.14%), 21 patients (12.8%) in Santa Fe, and 9 patients in Buenos Aires (9.4%) (p < 0.001). Extensive retinitis was observed in 49 patients (66.2%) in Misiones, 39 patients (23.8%) in Santa Fe, and 12 patients (12.5%) in Buenos Aires (p < 0.001). Conclusion: The results indicate that there are differences in the clinical characteristics of ocular toxoplasmosis in patients from Misiones, Santa Fe, and Buenos Aires.

Spectral optical coherence tomography findings in an elderly patient with syphilitic bilateral chronic panuveitis.

PURPOSE: To report the spectral domain optical coherence tomography (SD-OCT) features of a focal retinitis in an elderly male patient with bilateral syphilitic panuveitis. OBSERVATIONS: In the left eye (LE), spectral domain SD-OCT images during the active period revealed hyperreflectivity extending through the full thickness of the retina with no individualization of the layers, except for the retinal pigment epithelium. Once the lesion healed, SD-OCT imaging revealed an inner retinal atrophy and a mild disruption of the retinal pigment epithelium. CONCLUSIONS AND IMPORTANCE: In our patient, treponemal infection seemed to produce full-thickness retinal damage with partial involvement of the retinal pigment epithelium. The severe retinal damage, in this case, led to a poorer visual outcome than in other forms of syphilitic retinal involvement.

Adalimumab Treatment in Patients with Vogt-Koyanagi-Harada Disease.

PURPOSE: To evaluate the clinical outcome and safety of adalimumab in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses. RESULTS: In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab. CONCLUSIONS: Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.

FUSARIUM SOLANI SUBRETINAL ABSCESS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA.

PURPOSE: To report on a case of Fusarium solani subretinal abscess in a patient with acute myeloid leukemia treated with an allogenic bone marrow transplant. METHODS: A 47-year-old male with a history of acute myeloid leukemia with intermediate cytogenetic risk was admitted in our hospital. The disease relapsed after two cycles of chemotherapy. He was then treated with an allogenic bone marrow transplant, with busulfan, cyclophosphamide, and thymoglobulin. One week after the procedure, a sepsis of unknown origin in neutropenia occurred. Blood cultures and sputum were negative for bacteria and fungi. At the eighth week after the procedure, the patient had acute vision loss of the right eye. Funduscopy in the right eye revealed an inferior temporal yellowish white elevated lesion of approximately 10 disk areas and superficial perifoveal and perilesional hemorrhages. RESULTS: Vitrectomy was performed and samples from the vitreous and the subretinal abscess material were sent for analysis. Vitreous and subretinal specimens grew colonies of a fungus morphologically consistent with F. solani. CONCLUSION: Fusarium solani should be included in the differential diagnosis of subretinal abscesses.

Spectrum and visual outcomes of Vogt-Koyanagi-Harada disease in Argentina.

AIM: To review all cases of Vogt-Koyanagi-Harada (VKH) disease in an Inflammatory Eye Disease Service in Argentina and to describe the clinical profile and outcomes of treatment. METHODS: The records from patients with VKH disease between January 1980 and December 2008 were retrospectively analyzed for clinical profile, complications, and treatment. Patients were classified according to their initial treatment in group 1: high corticosteroid dose [≥1 mg/(kg·d)] within 2wk of illness onset; group 2: high corticosteroid dose, 2 to 4wk of onset and group 3: patients who received the high dose after 1mo of illness onset, patients who received lower oral doses than 1 mg/(kg·d) without regarding the time of beginning of the disease. RESULTS: A total of 210 eyes of 105 patients were included. The mean age at presentation was 32.6±13y (range: 10-74y), and 86.7% were female. The mean duration of follow up was 144±96.6mo. Patients in the group 1 had significantly higher visual acuity than the other groups (P<0.0001), none had (loss of, or no) light perception at the end of follow up, whereas 24.7% patients in group 3 ended in light perception (P<0.004). CONCLUSION: Patients with early high dose corticosteroid treatment have better visual acuity and fewer complications. Proper timing in referral and treatment is critical for better visual outcome in VKH disease.

Chronic Anterior Uveitis in Children.

PURPOSE: To describe the visual prognosis and remission rate of chronic anterior uveitis in pediatric patients. METHODS: A retrospective case series of children with chronic anterior uveitis treated in the University of Buenos Aires. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Uveitis remission was defined according to SUN criteria. RESULTS: There were 35 pediatric patients (61 eyes), mean age of uveitis onset was 7.69 ± 3 years, 60% were females and 74% had bilateral disease, median follow-up was 60 months (range: 12-192 months). JIA was more frequent in females (80.95 vs 21.43; p<0.0001) and oligoarthritis was the most common form. Remission rate was higher in males (HR = 4.99; 95% CI = 1.16-21.51; p = 0.031). More than 40 eyes remained with the same BCVA at 1 year of follow-up. CONCLUSIONS: Although remission was not common and only occurred after long-term follow-up, visual prognosis was good Received 30 August 2015; revised 6 March 2016; accepted 14 March 2016; published online 18 May 2016.

Tuberculous Subretinal Abscess in a Non-HIV Patient with Miliary Tuberculosis.

This case report describes the features of a tuberculous subretinal abscess in a non-HIV patient. It includes the characterization of the lesion with spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence examination. SD-OCT and autofluorescence imaging showed external retinal involvement during development of the tuberculous subretinal abscess. Patients with tuberculous lesions need a multidisciplinary approach, since the disease may involve any part of the body. In this case in particular, incidental findings at computed tomography scan led to the detection of this rare ocular manifestation of tuberculous disease.

Atypical Bilateral Fuchs Uveitis: Diagnostic Challenges.

UNLABELLED: Bilateral Fuchs uveitis associated with vitreous infiltration and posterior segment involvement requires a thorough diagnostic evaluation. The lack of well-defined diagnostic criteria makes identification of this entity difficult. The aim of this case report was to present the characteristics of a patient with atypical Fuchs uveitis and the procedures needed to rule out the differential diagnosis with specific attention to the utility of in vivo confocal microscopy (IVCM). CASE REPORT: One case of chronic bilateral uveitis with severe vitreous opacities is presented. After extensive systemic workup, including vitrectomy, the case had no identifiable systemic etiology. IVCM of the cornea revealed the presence of dendritiform keratic precipitates. CONCLUSION: The diagnosis of Fuchs uveitis is based on clinical findings as no confirmatory laboratory tests are available. A high index of suspicion is key to an early diagnosis, especially in the cases with vitreous opacities and posterior segment manifestations. Auxiliary tests such as IVCM may aid the clinician in the diagnosis of Fuchs uveitis.

Endogenous Histoplasma capsulatum endophthalmitis in an immunocompetent patient.

PURPOSE: To report on a case of Histoplasma capsulatum endogenous endophthalmitis in an immunocompetent patient. METHODS: A 30-year-old patient was admitted with floaters and vision impairment of 1 month's duration. He had a history of adrenal insufficiency, together with nasal, septum, and soft palate lesions of 3 months; duration. Culture results from specimens of these lesions were positive for H capsulatum. He was human immunodeficiency virus negative and there was no evidence of immunodepression or history of immunosuppression. Fundus examination revealed multiple fluffy balls with a string of pearls appearance, 2+ vitreous haze, multiple foci of retinochoroiditis inferiorly in the peripheral retina, and a 6-disk area lesion of retinochoroiditis at the superotemporal periphery. Due to poor response to oral itraconazole, a vitrectomy was performed with an intraocular injection of amphotericin B 5 µg/0.1 mL and removal for a vitreous specimen for culture of bacteria and fungi. RESULTS: Vitreous specimen culture of the yeast at 28°C grew a white filamentous fungus colony, which was again cultured in a brain heart infusion agar medium, where it developed hyaline septate hyphae with microconidia and circular macroconidia with double wall, which was stained with a lactophenol dye at microscopic examination. The macroscopic morphology was consistent with H capsulatum. CONCLUSIONS: Although endogenous H capsulatum endophthalmitis is a rare entity, it should be considered as a possible etiology even in apparently immunocompetent hosts, especially in patients with history of disseminated disease.