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.

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.

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.

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.

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.

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.

Long-term, drug-free remission of sympathetic ophthalmia with high-dose, short-term chlorambucil therapy.

OBJECTIVE: To evaluate the safety and effectiveness of short-term, high-dose chlorambucil therapy in achieving long-term, drug-free remission in the treatment of sympathetic ophthalmia (SO). DESIGN: Retrospective case series. PARTICIPANTS: Sixteen patients with SO treated with high-dose, short-term chlorambucil therapy between 1970 and 2010. METHODS: Descriptive and bivariate analyses were used to characterize disease and outcomes. MAIN OUTCOME MEASURES: Months of disease-free remission, prevalence rate of relapse, and prevalence of serious treatment-related adverse events. RESULTS: Sixteen patients with SO treated with short-term, high-dose chlorambucil were identified. Patients were treated with chlorambucil for a median of 14.0 weeks (mean, 14.5 weeks; range, 12.0-19.0 weeks). Median follow-up was 98.5 months (mean, 139.1 months; range, 48-441 months) from initiation of chlorambucil therapy. Control of inflammation was achieved in 100% of patients. Thirteen patients (81.3%) maintained vision of 20/40 or better in the sympathizing eye. Four patients (25%) relapsed after a median of 83 months (mean, 131 months) after cessation of systemic therapy. Seventy-five percent of relapses were controlled with topical therapy only. Conjunctival Kaposi's sarcoma developed in 1 patient. No patient demonstrated systemic malignancy. CONCLUSIONS: Short-term, high-dose chlorambucil therapy provides sustained periods of drug-free remission. With median follow-up of more than 8 years (mean, 11.6 years; range, 4-37 years), there was a low rate of recurrence and minimal long-term serious health consequences or adverse events. Because SO may be a lifelong condition and because chlorambucil therapy may offer long-term, drug-free remission, this treatment may be worth considering early in the decision-making process for severe sight-threatening disease.

Chronic postoperative Mycobacterium gordonae endophthalmitis in a patient with phakic intraocular lens.

METHODS: Case description of a 34 year old woman with chronic granulomatous anterior uveitis following implantation of a phakic anterior chamber intraocular lens (IOL). Aqueous humor was processed for bacterial, fungal culture, and PCR analysis. RESULTS: PCR for 16S ribosomal RNA universal primers was positive and Southern-blot for Propionibacterium spp was negative. Panfungal PCR was negative. Growth of a pigmented yellow colony was detected on Lowenstein-Jensen medium. The isolate was subsequently identified as Mycobacterium gordonae. The patient was treated for atypical mycobacteria as well as an intracameral injection of moxifloxacin, with resolution of inflammation and improvement in visual acuity. CONCLUSIONS: This is the first reported case of Mycobacterium gordonae chronic postoperative endophthalmitis, and of chronic endophthalmitis following phakic IOL surgery. PCR and cultures were invaluable in making the diagnosis.

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

PURPOSE: To assess the outcomes of the intravitreal administration of methotrexate in uveitis. METHODS: Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. RESULTS: Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. CONCLUSION: In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

Intravitreal bevacizumab for choroidal neovascularization secondary to Vogt-Koyanagi-Harada syndrome.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is characterized by bilateral diffuse uveitis associated with auditory, neurological, and cutaneous signs and symptoms. VKH syndrome is a cell-mediated autoimmune disease against melanocytes. Choroidal neovascularization (CNV) occurs in 15% of VKH patients and is associated with poor visual prognosis. CASES: We report on two patients with VKH syndrome and CNV that were treated with intravitreal bevacizumab. OBSERVATIONS: One of the VKH patients also had an extrafoveal CNV membrane and underwent multiple intravitreal injections of bevacizumab in combination with laser photocoagulation, with subsequent improvement in visual acuity. The second had a subfoveal CNV that responded to a single intravitreal injection of bevacizumab. CONCLUSION: Intravitreal bevacizumab may be a useful drug to treat CNV in eyes with VKH syndrome.

Diagnostic approaches to severe, atypical toxoplasmosis mimicking acute retinal necrosis.

PURPOSE: To describe the means of diagnosis and clinical features of atypical toxoplasmic chorioretinitis mimicking acute retinal necrosis. DESIGN: Observational case series. PARTICIPANTS: Twenty-two patients (25 eyes) with widespread chorioretinitis resulting from toxoplasmosis examined between 1990 and 2001. TESTING: Patients were diagnosed by various techniques, including polymerase chain reaction (PCR) of aqueous and vitreous, serum and intraocular antibody determination, culture of intraocular fluid, retinal biopsy, histopathologic examination, therapeutic trial of antibiotics active against toxoplasmosis, or a combination thereof. MAIN OUTCOME MEASURES: The primary outcome measure was diagnosis of disseminated toxoplasmic chorioretinitis by any combination of tests or by empiric use of specific antibiotics. The secondary outcome measure was visual and anatomic outcome of treatment. RESULTS: Mean age was 53.5 years (range, 19-77 years), with a median of 59.5 years. There were 9 women and 13 men. Six patients were infected with HIV, and 3 patients, 1 with HIV, had bilateral disease. Mean initial vision was 20/110 (median, 20/400; range, 20/20 to no light perception [NLP]). Sixteen patients (73%) had received oral or injectable corticosteroids and 11 (50%) had received antiviral therapy before the diagnosis of toxoplasmosis. Diagnosis was made solely by clinical response to antitoxoplasmosis medications in 4 patients. Sixteen patients were diagnosed based on evaluation of intraocular fluids and tissue by antibody determinations, culture, PCR, histopathologic examination, or a combination thereof. Visual acuity improved after treatment in 7 of 25 eyes (28%). Mean final visual acuity was 20/156 (median, 20/2500; range, 20/30 to NLP). Anatomically, 18 of 23 eyes with follow-up had healed or improved chorioretinitis. Retinitis was progressive in 1 eye, 2 eyes were enucleated, and 2 were phthisical. CONCLUSIONS: Diagnosis of atypical toxoplasmic chorioretinitis that mimics viral retinitis can be accomplished by several means. Prompt diagnosis may help avoid poor visual and anatomic outcomes after prolonged initial treatment with oral prednisone or antiviral medications.