Ibrutinib-Related Uveitis in Non-Hodgkin Lymphoma Patients: A Case Report and Literature Review.

PURPOSE: To report two cases of ibrutinib-related uveitis and review the literature to date. METHODS: We report two cases of ibrutinib-related uveitis using CARE guidelines and review the cases reported in the literature. RESULTS: Case 1) A 55-year-old female with recurrent primary central nervous system lymphoma presented with bilateral decreased visual acuity, photophobia, and floaters that started one month after initiating oral treatment with ibrutinib. Chronic non-granulomatous bilateral anterior-intermediate uveitis with macular edema was identified. Secondary causes were ruled out, and a presumptive diagnosis of ibrutinib-related uveitis was made. Case 2) A 57-year-old female with Waldenström macroglobulinemia who was treated with ibrutinib for two years presented with bilateral blurred vision, photophobia, red eyes, and floaters. A diagnosis of non-granulomatous, noninfectious panuveitis with bilateral cystoid macular edema was made. Secondary causes were ruled out, and ibrutinib toxicity was the most likely cause. CONCLUSION: Ibrutinib-related uveitis is a novel and under-diagnosed clinical entity. The most frequent clinical presentation in the literature is bilateral, non-granulomatous, anterior, and intermediate uveitis. Macular edema is a frequent complication. Uveitis usually requires topical treatment and the suspension of ibrutinib. Switching to second-generation Bruton tyrosine kinase inhibitors is proposed as a potential therapeutic alternative.

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.

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.

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.

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.

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.

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.

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.