Review of the Current Literature and Our Experience on the Value of OCT-angiography in White Dot Syndromes.

PURPOSE: To describe the application of OCT-A in various posterior uveitis disorders in our experience and to compare it with the available literature. METHODS: Eighteen eyes with the diagnoses of multifocal choroiditis (MFC), multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), tuberculous serpiginous-like choroiditis (SLC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSCR) were studied. RESULTS: We found flow void of the choriocapillaris in patients with APMPPE, SC, MFC, BSCR, and in SLC. In contrast, perfusion of the choriocapillaris seemed normal in patients with MEWDS. CONCLUSIONS: We confirmed that OCT-A contributes new information on the physiopathology of white dot syndromes and inflammatory chorioretinopathies, notably on whether or not the choriocapillaris is involved. Comparing the OCT-A features allowed us to suggest that both APMPPE and SLC might be part of the same spectrum of inflammatory disease with primary involvement at the level of the choriocapillaris and secondary RPE damage.

Laser Flare Photometry: A Useful Tool for Monitoring Patients with Juvenile Idiopathic Arthritis-associated Uveitis.

PURPOSE: We evaluated laser flare photometry (LFP) values in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Retrospective study. A decrease of the LFP value between baseline visit and 1 month after anti-inflammatory treatment intensification allowed us to define two groups of patients: group 1 (decreased LFP value ≥50%) and group 2 (<50%). We evaluated the prevalence of vision-threatening complications in both groups. RESULTS: Fifty-four patients (87 eyes) were followed for 9.9 ± 5 years. Group 1 eyes (n = 54) had significantly fewer ocular complications than group 2 eyes (n = 33) at both 5 years visit (p = .03) and final visit (p = .047). At the final visit, group 2 eyes had significantly more band keratopathy, trabeculectomy, cataract surgery, glaucoma and papille edema. Group 1 eyes kept a better visual acuity (p < .0001). CONCLUSION: The decrease of LFP values ≥50% of the initial value 1 month after treatment intensification is a good early prognostic factor.

Neoplasia and intraocular inflammation: From masquerade syndromes to immunotherapy-induced uveitis.

Masquerade syndromes represent a large set of ophthalmological entities that mimic inflammatory conditions. Any delay in their diagnosis may be correlated with systemic dissemination or worsening of the causal disease and, therefore, with poor prognosis. One of the disadvantages of the new potent treatments of uveitis is the delay that they can induce in the diagnosis of neoplastic intraocular infiltrations. Thorough and careful clinical examination of all patients referred for uveitis, especially when they are Caucasian, over 50 years of age, and with posterior segment involvement, is of paramount importance in this context. Ancillary investigations and often-invasive histo-pathologic evaluation of tissue specimens or ocular fluids are regularly required in these situations. The most common masquerade syndrome is primary vitreoretinal lymphoma (PVRL). New molecular diagnostic tools may be helpful in challenging cases lacking cytological confirmation. Therapeutic strategies targeting tumoral cells in the eye and also in the central nervous system can improve the life expectancy of affected patients. In this review, we discuss diagnostic strategies and current therapies in PVRL and provide an overview of other conditions that can mimic primary ocular inflammation, especially in the field of oncology and its new therapeutic armamentarium.

Clinical and Biological Factors Associated With Recurrences of Severe Toxoplasmic Retinochoroiditis Confirmed by Aqueous Humor Analysis.

PURPOSE: To investigate clinical and biological factors influencing recurrences of severe toxoplasmic retinochoroiditis (TRC) confirmed by aqueous humor analysis. DESIGN: Retrospective case series. METHODS: Retrospective analysis of 87 subjects with severe TRC, proven by positive Goldmann-Witmer coefficient (GWC), Toxoplasma gondii (T. gondii) immunoblot, or T. gondii-specific polymerase chain reaction (PCR) in aqueous humor. Cases with immunosuppression or retinal scars without previous recorded episode were excluded. Time-dependent, clinical, treatment-related, and biological factors were explored by univariate and multivariate shared frailty survival analyses. RESULTS: Among 44 included subjects (age, 40.4 ± 17.6 years; follow-up, 8.3 ± 2.7 years), 22 presented recurrences. There was 0.11 recurrence/patient/year and mean disease-free interval was 5.0 ± 2.9 years. The risk of recurrence was higher immediately after an episode (P < .0001). Among recurrent cases, the risk of multiple recurrences was higher when the first recurrence occurred after longer disease-free intervals (P = .046). In univariate analysis, the recurrence risk declined with higher number of intense bands on aqueous T. gondii immunoblot (P = .006), and increased when venous vasculitis was present initially (P = .019). Multivariate analysis confirmed that eyes with more intense bands on immunoblot had fewer recurrences (P = .041). There was a near-significant risk elevation after pyrimethamine/azithromycin treatment (P = .078 and P = .054, univariate and multivariate). Intravenous corticosteroid administration, oral corticosteroid administration, aqueous GWC, and T. gondii PCR did not influence recurrences (P = .12, P = .10, P = .39, and P = .96, respectively). CONCLUSIONS: Recurrences of severe TRC are not random and may be influenced by clinical and biological factors possibly related to blood-retinal barrier alterations. These results may contribute to identifying biomarkers for TRC reactivation.

Superficial and deep retinal foveal avascular zone OCTA findings of non-infectious anterior and posterior uveitis.

PURPOSE: To compare the superficial (FAZ-S) and deep foveal avascular zones (FAZ-D) of non-infectious anterior and posterior uveitis to healthy controls, using optical coherence tomography angiography (OCTA). METHODS: OCTA was performed on 74 eyes: 34 eyes with non-infectious posterior uveitis (with (post+CME) and without macular edema (post-CME)), 11 eyes with non-infectious anterior uveitis (with (ant+CME) and without macular edema (ant-CME)), and the control group which included 29 healthy eyes. RESULTS: Eyes suffering from non-infectious posterior uveitis presented with significantly larger FAZ-D when compared to healthy controls, both in the presence or in the absence of macular edema (p < 0.001). In the presence of macular edema, eyes presenting with anterior uveitis (ant+CME) also showed significantly larger FAZ-S (p = 0.03) and FAZ-D (p < 0.001), when compared to healthy controls. In the absence of macular edema, eyes with anterior uveitis cannot be distinguished from controls (p > 0.6). CONCLUSION: The deep retinal foveal avascular zone seems to be enlarged in eyes presenting with non-infectious posterior uveitis, both in the presence or absence of macular edema.

Angiographic Signatures of the Predominant Form of Familial Transthyretin Amyloidosis (Val30Met Mutation).

PURPOSE: To describe abnormalities in choroidal and retinal vasculature associated with Val30Met familial transthyretin amyloidosis (V30M-FTA) using fluorescein and indocyanine green (ICG) angiography. DESIGN: Prospective, cross-sectional study. METHODS: This study was conducted at the French National Reference Center for FTA. We included 18 consecutive genetically confirmed V30M-FTA patients (36 eyes) who underwent complete neurologic examination, including staging with polyneuropathy disability (PND) score, and complete ophthalmic evaluation, including staging of intraocular amyloid deposits and fluorescein and ICG angiograms (ICG-A). The grading of choroidal and retinal angiopathy, and their association with neurologic functional impairment, were the main outcome measures. RESULTS: Eleven men and 7 women, mean age 61.6 ± 12.1 years, were included. Retinal amyloid angiopathy (RAA) was detected in 24 eyes (92%) of 13 patients, with microaneurysms, retinal hemorrhages, and retinal ischemia of variable extent. Three patients (5 eyes) had neovascular glaucoma and 2 (2 eyes) had preretinal neovascularization. ICG-A indicated choroidal amyloid angiopathy (CAA) in all patients, with 3 distinct patterns-diffuse (9/18 patients), focal (5/18 patients), or punctiform (4/18 patients)-based on the extent of late hypercyanescence along the choroidal arteries. PND scores were significantly higher in patients with diffuse CAA (firework pattern) compared to those with limited CAA (focal and punctiform patterns) (2.89 vs 1.78, P = .045). CONCLUSION: RAA is a frequent and severe complication of V30M-FTA that may lead to anterior and posterior segment neovascularization. CAA was detected in all patients, with a late hypercyanescent delineation of the choroidal arterial vasculature, which was more extensive with increased disease severity.

Cataract Surgery with Primary Lens Implantation in Children with Chronic Uveitis.

PURPOSE: To evaluate the evolution of chronic uveitis in children undergoing cataract surgery with primary intraocular lens (IOL) implantation. METHODS: Twelve children with chronic uveitis underwent cataract surgery with primary posterior chamber intraocular lens (IOL) implantation. RESULTS: Fourteen eyes were implanted with a foldable hydrophobic acrylic IOL. The mean follow-up was 35.39 months (8.72-69.57). The mean BCDVA before surgery and at the end of follow-up was 1.11 (0.40-2.30; SD: 0.57) and 0.48 (0-3; SD: 0.77; p=0.007) respectively. The mean oral corticosteroids dosage after surgery and at the end of follow-up was 0.80 mg/kg/day (SD: 0.37) and 0.17 mg/kg/day (SD: 0.24; p=0.001) respectively. All patients except one were treated with methotrexate. Four patients (5 eyes) were additionally treated with anti-tumor necrosis factor agent. CONCLUSIONS: Cataract surgery with primary posterior chamber hydrophobic IOL implantation is possible and leads to a good visual recovery in cases of pediatric chronic uveitis. This surgery requires aggressive anti-inflammatory management with immunosuppressive drugs to control inflammation and reduce the corticosteroids dosage.

Regulatory T Cell Therapy for Uveitis: A New Promising Challenge.

Uveitis is a sight-threatening primary intraocular inflammation of various origins in mainly young and active patients. Due to the absence of biomarkers in most of the cases, the current treatment of noninfectious entities remains nonspecific, using corticosteroids, conventional immunosuppressors, and more recently biological agents. Identification of regulatory T cells in different models of autoimmune uveitis together with the evaluation of this important subpopulation in different entities paved the way for new therapeutic strategies, in addition to exclusive pharmaceutical approaches. Upregulation of regulatory T cells induced by biological agents has been recently highlighted. Development of cell therapy in autoimmune diseases is at its stammering needing more experimental data and robust clinical trials to demonstrate safety and efficacy before larger developments. Specific or polyclonal Tregs may be used, but it is of utmost importance to determine the method of selection, the level of activation, and the route of administration. Mastering immune cell therapy remains a challenging goal in patients with autoimmune diseases, but it may significantly enlarge our therapeutic possibilities in severe and refractory situations.

Rabbit hunter uveitis: case report of tularemia uveitis.

BACKGROUND: Literature reports on ophthalmological manifestations related to tularemia, a zoonose caused by the bacterium Francisella tularensis, largely refer to Parinaud's oculoglandular syndrome, which consists of the association of conjunctivitis with preauricular lymphadenitis. In this paper, we report a case of intraocular inflammation during tularemia infection. CASE PRESENTATION: A 52-year-old Caucasian man was diagnosed with unilateral uveitis. The uveitis was posterior, with a 2+ vitritis and a large yellowish lesion involving the macula with an overlying sub-retinal detachment, extending inferiorly, and subretinal hemorrhages. Fluorescein angiography showed a late hyperfluorescence with focal vascular leakage. Ultrasound biomicroscopy confirmed the presence of a 3.8 mm parietal granuloma with a few calcifications in the left eye. While extensive work-up eliminated any other infectious and non-infectious etiology, tularemia was diagnosed by advanced serology consisting of two-dimensional Western-immunoblotting. The patient, a hunter, recalled having killed rabbits in the days before the symptoms appeared. Uveitis was rapidly controlled following treatment with doxycycline, yet three years after initiation of the treatment, the patient still complained of loss of vision in the left eye with a central scotoma. CONCLUSIONS: Posterior uveitis may be an infrequent manifestation of tularemia infection, and therefore this infection should be considered in the differential diagnosis of intraocular inflammation in areas where F. tularensis is endemic.

PERSISTENT PLACOID MACULOPATHY IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the case of a patient presenting with persistent placoid maculopathy imaged with optical coherence tomography angiography. METHODS: Case report of a 72-year-old man who presented with blurred vision in his right eye. fundus photography, fluorescein angiography, infracyanine green angiography, fundus autofluorescence imaging, spectral domain optical coherence tomography, optical coherence tomography angiography, and split spectrum amplitude decorrelation angiography were performed. The diagnosis was made based on ophthalmological manifestations and multimodal imaging. RESULTS: The spectral domain optical coherence tomography image of the right eye revealed disruption of the ellipsoid layers, and an underlying sliver of hyporeflectance. In the left eye, there were no obvious changes on spectral domain optical coherence tomography. In both eyes, infracyanine green angiography showed hypocyanescence of the lesions, persisting throughout late phases. In optical coherence tomography angiography, imaging of the choroidal capillary layers revealed hyposignal lesions, topographically corresponding exactly to hypocyanescent lesions on infracyanine green angiography. CONCLUSION: In this patient, a distinct hyposignal on optical coherence tomography angiography, combined with hypocyanescence on infracyanine green angiography, was interpreted as indicating focal hypoperfusion of the choriocapillaris.

Treatment of Uveitis by In Situ Administration of Ex Vivo-Activated Polyclonal Regulatory T Cells.

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell therapy is a promising approach for the treatment of autoimmune diseases. To be effective, Treg cells should be in an activated state in the target tissue. This can be achieved by systemic administration of Ag-specific Treg cells, which are difficult to produce in conditions that can be translated to the clinic. In this paper, we propose an alternative approach consisting of in situ injection of preactivated polyclonal Treg cells that would exert bystander suppression in the target tissue. We show that polyclonal Treg cells suppressed uveitis in mice as efficiently as Ag-specific Treg cells but only when preactivated and administered in the vitreous. Uveitis control was correlated with an increase of IL-10 and a decrease of reactive oxygen species produced by immune cell infiltrates in the eye. Thus, our results reveal a new mechanism of Treg cell-mediated suppression and a new Treg cell therapy approach.

Foveal Serous Retinal Detachment in Juvenile Idiopathic Arthritis-associated Uveitis.

PURPOSE: In juvenile idiopathic arthritis (JIA)-associated uveitis complicated by foveal serous retinal detachment (FSRD), we documented the relationship between best corrected visual acuity (BCVA), level of anterior chamber flare and OCT features. METHODS: Nine children (15 eyes) with FSRD were identified among 38 children with JIA-associated maculopathy. Outcome measures included BCVA, ocular inflammatory activity quantified by laser flare photometry and the macular profile analyzed by OCT. RESULTS: The diagnosis of FSRD led to intensification of the treatment using subtenon's injection of triamcinolone or systemic immunomodulatory therapy. The improvement of BCVA at presentation (0.46 logMAR) was significant at 36 months follow-up (0.15 logMAR). The resolution of FSRD along with visual improvement (p = 0.0032) correlated with improvement in anterior chamber flare (p = 0.01). CONCLUSION: FSRD is a complication of chronic JIA-associated uveitis that responds well to intensification of immunomodulation. Visual improvement is correlated with FSRD resolution and with flare photometry values.

Ocular Manifestations of X-linked Chronic Granulomatous Disease: About Two Atypical Case Reports.

PURPOSE: Two atypical cases of ocular localizations of chronic granulomatous disease are reported. METHODS: The first case is about a 22-year-old woman carrier of the disease who developed active intraocular inflammation and choroidal granulomas successfully treated by steroids. The second is about a 2-year-old boy consulting for unilateral anterior uveitis and subsequent anterior chamber granuloma development as first signs of the disease. RESULTS: X-linked chronic granulomatous disease is a rare inherited primary immunodeficiency syndrome characterized by disorders of phagocytic cells resulting in recurrent infections and development of granulomas. Ophthalmological manifestations are not rare and are mainly represented by surface and intraocular inflammation with possible choroidal granulomas. The two cases reported here are atypical, one of active inflammation in a carrier and the other revealing the disease. CONCLUSION: Ophthalmologists must be aware of chronic granulomatous disease and the possible ocular involvement of this disorder.

Combined fluorescein angiography and spectral-domain optical coherence tomography imaging of classic choroidal neovascularization secondary to age-related macular degeneration before and after intravitreal ranibizumab injections.

PURPOSE: To evaluate the combined fluorescein angiography and spectral-domain optical coherence tomography features in a consecutive series of exudative age-related macular degeneration eyes with classic choroidal neovascularization before and after anti-vascular endothelial growth factor treatment. METHODS: Retrospective interventional study. All consecutive patients with exudative age-related macular degeneration because of newly diagnosed classic choroidal neovascularization visited during 3 months and treated by intravitreal ranibizumab injection on "as-needed" basis were analyzed. Combined fluorescein angiography and spectral-domain optical coherence tomography examination (Spectralis Heidelberg Retina Angiograph OCT) was performed at baseline and at the 12-month follow-up visit. RESULTS: Twenty-nine treatment-naive eyes (29 patients, 10 men and 19 women, mean age 76.28 ± 10.86 years) were included. A mean of 5.3 ± 3.5 injections was administered during 12 months. At Month 12 visit, patients showed an improved best-corrected visual acuity (P = 0.01), a reduction of linear dimension of the entire lesion on fluorescein angiography (P = 0.02), and a reduction of the entire lesion width on spectral-domain optical coherence tomography (P < 0.001). At baseline, in all cases we distinguished on spectral-domain optical coherence tomography scan a highly reflective subretinal lesion, above and separate from the retinal pigment epithelium. The highly reflective subretinal lesion showed a significant reduction of width along the length of a single B-scan, at Month 12 follow-up visit (P < 0.001). It is notable that a small "discreet" pigment epithelial detachment associated with the highly reflective subretinal lesions was present in 28 of 29 eyes at baseline and after treatment (at Month 12 follow-up visit). CONCLUSION: A discreet pigment epithelial detachment represents a common associated finding of classic choroidal neovascularization. Our study demonstrated that anti-vascular endothelial growth factor treatment may not only stop the growth of the highly reflective subretinal lesion that colocalize with the classic choroidal neovascularization but also determine its regression.

Cataract surgery with primary intraocular lens implantation in children with uveitis: long-term outcomes.

PURPOSE: To report long-term outcomes of cataract surgery with primary posterior chamber intraocular lens (IOL) implantation in children with chronic uveitis. SETTING: Department of Ophthalmology, Pitié-Salpêtrière Hospital, Paris, France. DESIGN: Case series. METHODS: This case series comprised patients younger than 16 years with chronic uveitis who underwent phacoemulsification with primary implantation of a heparin surface-modified poly(methyl methacrylate) posterior chamber IOL in the capsular bag. The intraocular inflammation was fully controlled for at least 3 consecutive months before surgery in all cases. The main outcome measures were final corrected distance visual acuity (CDVA), postoperative inflammation, complications, and level of immunosuppressive treatment. RESULTS: Twenty-two eyes of 16 children (7 girls, 9 boys; median age at surgery 9.5 years old) were included. Underlying uveitic entities were juvenile idiopathic arthritis in 9 patients; idiopathic uveitis in 4; and Behçet disease, sarcoidosis, and varicella zoster-associated uveitis in 1 patient each. The final CDVA was 0.3 logMAR or better in all cases. Postoperative complications included posterior capsule opacification requiring laser capsulotomy in 2 eyes, glaucoma in 4 eyes, and cystoid macular edema/macular dysfunction in 3 eyes. The mean dose of oral prednisone was 29.5 mg/day preoperatively and 8.13 mg/day at the last follow-up. The median follow-up was 6 years (range 5 to 19 years). CONCLUSION: The results indicate that uveitis is not a formal contraindication to primary IOL implantation in the management of pediatric cataract surgery in cases with full control of intraocular inflammation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Ocular modifications in a young girl with cryopyrin-associated periodic syndromes responding to interleukin-1 receptor antagonist anakinra.

An 8-year-old patient with genetically confirmed chronic infantile neurological cutaneous and articular syndrome was treated with interleukin-1 receptor antagonist, anakinra. She initially presented with recurrent episodes of fever, rash, chronic fatigue, frequent headaches, ocular involvement (corneal infiltrate and papillary edema), and permanent increased biologic inflammatory markers. Following treatment with anakinra, all symptoms and inflammation resolved. Ophthalmologic signs normalized. This ophthalmologic description (optic nerve and cornea) has never been illustrated, even if ocular affections are classic in the cryopyrin-associated periodic syndromes.

Intravitreal bevacizumab as first local treatment for uveitis-related choroidal neovascularization: long-term results.

PURPOSE: To report long-term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis. METHODS: Files of patients receiving 1.25 mg/0.05 ml bevacizumab as primary local treatment for CNV were retrospectively reviewed. Main outcomes were change in best-corrected visual acuity (BCVA) and central foveolar thickness (CFT), treatment-related adverse events, and number and frequency of injections. RESULTS: Fifteen eyes from fifteen patients were included. Multifocal choroiditis and panuveitis were the diagnosis in seven, ampiginous choroiditis in two, and for six remaining, serpiginous choroiditis, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, punctuate inner choroidopathy, tuberculosis and idiopathic inflammation. In 13 eyes, neovascularization was subfoveal, and peripapillary in two. Intraocular inflammation was strictly controlled in all cases by the time of injections. BCVA improved from logMar 0.53 to logMar 0.29 in 12 eyes (80%), while CFT decreased from 239.06 to 195.2 µm in 13 (87%). Twelve eyes received more than one injection; mean number in this group was 4.25 (2-8), and frequency 1 every 12.97 weeks. There were no adverse events related to bevacizumab or the procedure. Median follow-up was 17.6 months (8-25). CONCLUSIONS: First-intention IVT bevacizumab for inflammatory CNV showed transient improvement in BCVA and CFT, in eyes under controlled inflammation. Reinjection was needed in most cases. Further work should conclude about safety related to repeated injections.

Bilateral fungal endophthalmitis masquerading as multifocal chorioretinitis.

PURPOSE: Spontaneous healing of ocular Candida infection is extremely rare, and early clinical manifestations may be misleading. This report explicates how to make the appropriate diagnosis when facing atypical presentation of the disease. METHODS AND PATIENTS: Case report. RESULTS: A 36-year-old woman presented with bilateral chorioretinitis. Intravenous drug abuse was not suspected, and a diagnosis of multifocal chorioretinitis was made. Oral corticosteroid treatment was started. Three months later, all previously seen lesions had healed on the right eye but had increased on the left with development of severe endophthalmitis. Microbiologic analysis of scalp pustules yielded Candida albicans. She underwent vitrectomy, intravitreous amphotericin B injection, and systemic fluconazole treatment. The uveitis responded well to this treatment regiment, but subsequent development of macular edema and retinal detachment in the left eye limited the final visual acuity to 20/200. Visual acuity remained 20/20 on the right without any evidence of inflammation. CONCLUSION: This case demonstrates a broad range of potential outcomes after Candida endophthalmitis in the same patient, from very rare healing without antifungal treatment in one eye to severe panuveitis in the other eye. The delayed diagnosis in this case led to the inappropriate treatment with corticosteroids alone and delayed antifungal treatment. Early differentiation of Candida chorioretinitis from multifocal chorioretinitis is critical to final visual outcome.