Cristobal Couto

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

BackgroundVogt-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.CasesWe report on two patients with VKH syndrome and CNV that were treated with intravitreal bevacizumab.ObservationsOne 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.ConclusionIntravitreal bevacizumab may be a useful drug to treat CNV in eyes with VKH syndrome.

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 Kaposis 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.

Reactivation of Ocular Toxoplasmosis in Non-Hispanic Persons, Misiones Province, Argentina.

To the Editor: Ocular toxoplasmosis (OT), caused by the parasite Toxoplasma gondii, is known to be a major health problem in South America, especially in Colombia and Brazil (1–3). The highest prevalence of OT has been reported in Erechim, Rio Grande do Sul, Brazil, a state that borders Uruguay and Argentina, where a representative population-based household survey showed that 17.7% of 1,042 adults examined had OT (1). For comparison, it is estimated that ≈2% of T. gondii–infected persons in the United States manifest OT (4). It is still unclear whether the high rate of OT in South America is attributable to host or parasite genetic factors or differences in exposure rate (5,6). In the province of Misiones in Argentina, the prevalence of OT in patients seeking care in an ophthalmic office is also high and has been documented as high as 20% (7). The area was mostly settled in the early 20th century by non-Hispanic European immigrants from Germany and Slavic countries who arrived through Southern Brazil. We explored the relationship between ethnic origin and frequency of reactivation toxoplasmic retinochoroiditis (RTR) in patients who sought care in a private secondary care eye clinic in Obera, Misiones, Argentina, during February 2004–May 2014. All patients with uveitis were examined by a single uveitis specialist (M.R.), who performed complete ophthalmological examinations, including visual acuity, anterior biomicroscopy, tonometry, and indirect ophthalmoscopy. Study inclusion criteria were presence of RTR in 1 or both eyes and specific T. gondii IgG in blood serum samples. A minimum of 3 months with no signs of intraocular inflammation was required to differentiate chronic active retinochoroiditis from 2 consecutive episodes of RTR. The study included 112 nonimmunosuppressed patients with RTR. The patients completed a questionnaire including demographic data for the patient, as well as the first and last names and countries of origin of parents, grandparents, and great-grandparents. Informed consent was obtained from all participants and the study was approved by the human subjects review committee of Misiones Province. The patients were divided into 4 groups (Table): 1) patients reporting >1 ancestor born in Spain were considered Hispanic (n = 29); 2) patients without Hispanic ancestry who had >1 ancestor born in Poland, Ukraine, Russia, or Belarus, and who spoke Polish, Ukrainian, or Russian were considered Slavic (n = 28); 3) patients without Hispanic or Slavic ancestry who had >1 ancestor born in Germany or the Austro-Hungarian Empire and who spoke German were considered Germanic (n = 46); and 4) patients who did not fulfill the criteria of any of the above-mentioned groups were designated as others (n = 9). All patients had RTR at baseline; 28 had >1 more RTR episode during the follow-up period (Table). Multiple logistic regression analysis, in which Hispanic patients were used as a reference group, showed that Germanic and Slavic patients had a higher risk for reactivation during the follow-up period, but the odds ratio was significant only for Slavic patients after adjustment for rural dwelling. Table Demographic baseline characteristics of patients with reactivation of OT and multiple logistic regression analysis of the association between ethnic origin and risk for RTR during follow-up, Misiones province, Argentina, 2004–2014* More than 95% of Toxoplasma gondii strains in Europe belong to the clonal type II lineage, whereas strains from South America are genetically divergent and diverse (6,8). We hypothesize that the European population is poorly adapted to South American strains and therefore more susceptible to OT. If this hypothesis is true, Native Americans who had a long history of exposure to atypical strains from South America should be more resistant to OT. This hypothesis is reinforced by a recent survey conducted among Mbya-Guarani Indians, who had a serologic prevalence of toxoplasmosis 70%, but only 3.5% of them had toxoplasmic retinochoroidal lesions (M. Rudzinski, unpub. data). Argentineans have a large incidence of European genetic heritage in their Y-chromosomal and autosomal DNA, but ≈50% of their mitochondrial gene pool is of Native American ancestry (9). The amount of admixture between Europeans and Native Americans with inheritance of resistance genes to OT from Native Americans may explain the difference of susceptibility to RTR between Hispanic and non-Hispanic Europeans. Admixture events between Europeans and Native Americans mainly involved Hispanics whose migration to Argentina started in the 16th century and continued until the mid-20th century. Persons in Argentina who have Spanish surnames can carry as much as 80% Native American genetic ancestry (9,10). In contrast, the Slavic and German Europeans migrated to Misiones only during a large surge of European immigration between 1890 and 1950, and did not have substantial admixture with Native Americans. Despite the fact that this study was not a random or representative sample of all ethnic groups in Argentina and the Native American mixture of the patients was not known, and environmental and dietary influences were not examined, our results suggest host genetic factors as determinants of disease severity in OT.

Chronic postoperative mycobacterium gordonae endophthalmitis in a patient with phakic intraocular lens

Abstract 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.

Chronic Anterior Uveitis in Children

ABSTRACT 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

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 months 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.

Is reactivation of toxoplasmic retinochoroiditis associated to increased annual rainfall

Background: Reactivation of toxoplasmic retinochoroiditis is the most frequent form of uveitis in Misiones, Argentina. Fluctuations in the number of patients consulting with this type of uveitis were detected during the last decade. Since the province was consecutively exposed to rainy and dry periods over the last years, we decided to explore whether a relationship between reactivation of toxoplasmic retinochoroiditis and rain might be established according to the data registered during the 2004–2010 period. Results: The frequency of toxoplasmic reactivation episodes increases when precipitation increases (mostly in second and fourth trimesters of each year). Analysis of the independent variables demonstrates that precipitation is a significant predictor of the frequency of reactivation episodes. Although registered toxoplasmic reactivations were more frequent during the third trimester of the year, the association between the third trimester and the reactivation episodes did not reach statistical significance. Conclusion: Prolonged and intense rainfall periods were significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition on both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities are discussed.

Adalimumab Treatment in Patients with Vogt–Koyanagi–Harada Disease

ABSTRACT 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.

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

ABSTRACT 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.