EVALUATION OF TUMOR NECROSIS FACTOR INHIBITOR THERAPY IN SUSAC SYNDROME.

PURPOSE: To evaluate the effect of tumor necrosis factor (TNF) inhibitor therapy on ocular relapses in patients with Susac syndrome. METHODS: Multicenter retrospective cohort study of patients diagnosed with Susac syndrome according to classical clinical criteria. We evaluated the disease activity before and after introduction of anti-TNF therapy and its value as a steroid-sparing agent. RESULTS: Five patients were included. All were initially treated with a combination of corticosteroids and classical immunosuppressive drugs. Infliximab was started in three patients, and adalimumab was started in two patients. Patients had on average 5 ocular relapses during a mean follow-up time of 2.59 years before introducing a TNF inhibitor, corresponding with on average 1.93 relapses per year. After the introduction of an anti-TNF agent, this number was reduced by factor 5.51 to an average of 0.35 relapses per year for a mean follow-up of 2.86 years (P = 0.10). Before anti-TNF introduction ocular relapses occurred at a mean daily dose of 34 mg of prednisone, whereas with anti-TNF treatment, corticosteroid administration could be completely stopped in four patients with one patient still needing 5 mg daily (P = 0.10). Infliximab and adalimumab generally were well tolerated, and no serious adverse events were reported. CONCLUSION: Although not statistically significant, our results suggest that anti-TNF therapy can be a valuable option for the treatment of ocular Susac syndrome and may especially be considered in those patients unresponsive to more conventional immunosuppressive treatment.

Retinal endothelial cell phenotypic modifications during experimental autoimmune uveitis: a transcriptomic approach.

BACKGROUND: Blood-retinal barrier cells are known to exhibit a massive phenotypic change during experimental autoimmune uveitis (EAU) development. In an attempt to investigate the mechanisms of blood-retinal barrier (BRB) breakdown at a global level, we studied the gene regulation of total retinal cells and retinal endothelial cells during non-infectious uveitis. METHODS: Retinal endothelial cells were isolated by flow cytometry either in Tie2-GFP mice (CD31+ CD45- GFP+ cells), or in wild type C57BL/6 mice (CD31+ CD45- endoglin+ cells). EAU was induced in C57BL/6 mice by adoptive transfer of IRBP1-20-specific T cells. Total retinal cells and retinal endothelial cells from naïve and EAU mice were sorted and their gene expression compared by RNA-Seq. Protein expression of selected genes was validated by immunofluorescence on retinal wholemounts and cryosections and by flow cytometry. RESULTS: Retinal endothelial cell sorting in wild type C57BL/6 mice was validated by comparative transcriptome analysis with retinal endothelial cells sorted from Tie2-GFP mice, which express GFP under the control of the endothelial-specific receptor tyrosine kinase promoter Tie2. RNA-Seq analysis of total retinal cells mainly brought to light upregulation of genes involved in antigen presentation and T cell activation during EAU. Specific transcriptome analysis of retinal endothelial cells allowed us to identify 82 genes modulated in retinal endothelial cells during EAU development. Protein expression of 5 of those genes (serpina3n, lcn2, ackr1, lrg1 and lamc3) was validated at the level of inner BRB cells. CONCLUSION: Those data not only confirm the involvement of known pathogenic molecules but further provide a list of new candidate genes and pathways possibly implicated in inner BRB breakdown during non-infectious posterior uveitis.

Potential Interplay between Hyperosmolarity and Inflammation on Retinal Pigmented Epithelium in Pathogenesis of Diabetic Retinopathy.

Diabetic retinopathy is a frequent eyesight threatening complication of type 1 and type 2 diabetes. Under physiological conditions, the inner and the outer blood-retinal barriers protect the retina by regulating ion, protein, and water flux into and out of the retina. During diabetic retinopathy, many factors, including inflammation, contribute to the rupture of the inner and/or the outer blood-retinal barrier. This rupture leads the development of macular edema, a foremost cause of sight loss among diabetic patients. Under these conditions, it has been speculated that retinal pigmented epithelial cells, that constitute the outer blood-retinal barrier, may be subjected to hyperosmolar stress resulting from different mechanisms. Herein, we review the possible origins and consequences of hyperosmolar stress on retinal pigmented epithelial cells during diabetic retinopathy, with a special focus on the intimate interplay between inflammation and hyperosmolar stress, as well as the current and forthcoming new pharmacotherapies for the treatment of such condition.

MHC class II expression and potential antigen-presenting cells in the retina during experimental autoimmune uveitis.

BACKGROUND: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. METHODS: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals. MHC class II expression was studied by immunostainings on eye cryosections. For flow cytometry (FC) analysis, retinas were dissected and enzymatically digested into single-cell suspensions. Three MHC class II+ retinal cell populations were sorted by FC, and their RNA processed for RNA-Seq. RESULTS: Immunostainings demonstrate strong induction of MHC class II expression in EAU, especially in the inner retina at the level of inflamed vessels, extending to the outer retinal layers and the subretinal space in severely inflamed eyes. Most MHC class II+ cells express the hematopoietic marker IBA1. FC quantitative analyses demonstrate that MHC class II induction significantly correlates with disease severity and is associated with upregulation of co-stimulatory molecule expression. In particular, most MHC class IIhi cells express co-stimulatory molecules during EAU. Further phenotyping identified three MHC class II+ retinal cell populations: CD45-CD11b- non-hematopoietic cells with low MHC class II expression and CD45+CD11b+ hematopoietic cells with higher MHC class II expression, which can be further separated into Ly6C+ and Ly6C- cells, possibly corresponding to infiltrating macrophages and resident microglia. Transcriptome analysis of the three sorted populations leads to a clear sample clustering with some enrichment in macrophage markers and microglial cell markers in Ly6C+ and Ly6C- cells, respectively. Functional annotation analysis reveals that both hematopoietic cell populations are more competent in MHC class II-associated antigen presentation and in T cell activation than non-hematopoietic cells. CONCLUSION: Our results highlight the potential of cells of hematopoietic origin in local antigen presentation, whatever their Ly6C expression. Our work further provides a first transcriptomic study of MHC class II-expressing retinal cells during EAU and delivers a series of new candidate genes possibly implicated in the pathogenesis of retinal autoimmunity.

Involvement of TonEBP/NFAT5 in osmoadaptative response of human retinal pigmented epithelial cells to hyperosmolar stress.

PURPOSE: Macular edema, a frequently encountered complication of diabetic retinopathy (DR), results from alterations of the blood retinal barrier (BRB) and leads to modifications of the retinal pigmented epithelium (RPE) functions. Osmolar changes of the surrounding medium could be responsible for modifications of the RPE functions leading to disturbance of retinal homeostasis. The expression, activation and function of the key hyperosmolar response factor Tonicity Enhancer Binding Protein (TonEBP also called nuclear factor of activated T-cell 5 - NFTA5) was investigated in ARPE-19 cells, derived from human RPE, in response to hyperosmolar stimulation. METHODS: ARPE-19 cells were exposed to hyperosmolar medium. TonEBP mRNA and protein levels were quantified by qRT-PCR and semi-quantitative Western blot. TonEBP nuclear translocation was investigated by immunofluorescence. TonEBP transactivation activity was measured using a reported plasmid containing TonEBP binding sites. RESULTS: In response to hyperosmolar stimulation of ARPE-19 cells, a dose-dependent increase in TonEBP mRNA and protein levels, as well as TonEBP nuclear translocation were observed. TonEBP transactivation activity was further demonstrated using a reporter plasmid containing TonEBP binding sites. A dominant negative form of TonEBP abolished NaCl-induced increase in TonEBP transactivation activity, and inhibited the increase of the target genes aldose reductase and sodium-dependent taurine transporter mRNA levels. SB203580, an inhibitor of two of the p38 protein kinase's isoforms (p38α and p38ß) inhibited the TonEBP nuclear translocation and transactivation activity in ARPE-19 cells exposed to hyperosmolar stimulation. CONCLUSIONS: Our data demonstrates the involvement of TonEBP in the mechanisms responsible for osmoadaptation to hyperosmolar stress in RPE cells. Given the emerging role of TonEBP in different pathological pathways, these data open new perspectives for the analysis of the mechanisms involved in the modification of functions of the RPE during macular edema.

Aquaporin-1 expression in proliferative vitreoretinopathy and in epiretinal membranes.

PURPOSE: Aquaporin-1 (AQP1) is involved in cell migration and proliferation; therefore, the purpose of the study was to investigate its expression in proliferative vitreoretinopathy (PVR) and epiretinal membranes (ERM). METHODS: 19 membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and protein expressions were determined by RT-qPCR and immunofluorescence in the membranes from PVR and ERM. RESULTS: AQP1 mRNA and protein were expressed in both PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth muscle actin ( α SMA) and with glial fibrillary acidic protein (GFAP). There were a higher percentage of cells coexpressing AQP1 and α SMA than AQP1 and GFAP. GFAP and α SMA did not colocalize. CONCLUSION: Our data show for the first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by the α SMA-positive cells, presumably myofibroblasts, but also by GFAP-positive cells, assumed to be glial cells. These original findings warrant further functional investigations aiming at studying the potential role of AQP1 in cell migration and proliferation occurring during the development of PVR and ERM.

Subretinal Therapy: Technological Solutions to Surgical and Immunological Challenges.

Recent advances in ocular gene and cellular therapy rely on precisely controlled subretinal delivery. Due to its inherent limitations, manual delivery can lead to iatrogenic damage to the retina, the retinal pigment epithelium, favor reflux into the vitreous cavity. In addition, it suffers from lack of standardization, variability in delivery and the need to maintain proficiency. With or without surgical damage, an eye challenged with an exogenous viral vector or transplanted cells will illicit an immune response. Understanding how such a response manifests itself and to what extent immune privilege protects the eye from a reaction can help in anticipating short- and long-term consequences. Avoidance of spillover from areas of immune privilege to areas which either lack or have less protection should be part of any mitigation strategy. In that regard, robotic technology can provide reproducible, standardized delivery which is not dependent on speed of injection. The advantages of microprecision medical robotic technology for precise targeted deliveries are discussed.

Natural history of Usher type 2 with the c.2299delG mutation of USH2A in a large cohort.

BACKGROUND: The c.2299delG mutation is prevalent and accounts for 24.5% USH2A pathogenic variants, with promising prospects for customized gene therapy. MATERIALS AND METHODS: We compared the ocular and auditory phenotypes in a retrospective cohort of 169 Usher type 2 patients, with and without the c.2299delG allele, including visual acuity, slit-lamp examination, optical coherence tomography, kinetic perimetry, and audiometric assessment to define the hearing disability. Statistical methods used were covariate balancing propensity score and adjusted survival curves log-rank test for the analysis of visual acuity. RESULTS: We compare 54 Usher patients (31%) carrying at least one c.2299delG allele to 109 patients without this variant. The mean ages at onset of night blindness (14 years) and onset of peripheral vision deficiency (24 years) were similar in both groups, as was the severity of hearing loss (p = 0.731), even in homozygotes (p = 0.136). Based on the covariate balancing propensity score, the c.2299delG carrier patients developed cataract and reached a BCVA of 20/63 earlier than patients without this mutation (mean age 36 versus 42 y.o.; and 52.2 versus 55.1 y.o., respectively). Using adjusted survival curves and a log-rank test based on inverse probability weighting, patients with the c.2299delG variant reach blindness (BCVA <20/400) at 42.3 years old instead of 79.8 years for other USH2A pathogenic variants. CONCLUSIONS: We conclude that c.2299delG is associated with a more severe phenotype of the Usher type 2, in homozygotes and in compound heterozygotes.

Comparison of rubella virus- and herpes virus-associated anterior uveitis: clinical manifestations and visual prognosis.

PURPOSE: To compare the clinical characteristics and visual prognosis of patients with anterior uveitis (AU) and intraocular fluid analysis positive for rubella virus (RV), herpes simplex virus (HSV), or varicella zoster virus (VZV). DESIGN: Retrospective, observational study. PARTICIPANTS: The study included 106 patients with AU and positive polymerase chain reaction (PCR) results, Goldmann-Witmer coefficients (GWCs), or both, for RV (n = 57), HSV (n = 39), or VZV (n = 10). METHODS: Clinical records of the included patients were analyzed retrospectively; demographic constitution, ophthalmologic characteristics, and visual prognosis were compared. MAIN OUTCOME MEASURES: Age, gender, and diverse clinical and laboratory characteristics, including course and laterality of AU; prevalence of positive results for PCR, GWC, or both; conjunctival redness; corneal edema; history of keratitis; presence of keratic precipitates; synechiae; heterochromia; and grade of inflammation. In addition, complications and visual acuity at 1 and 3 years of follow-up were recorded. RESULTS: All 3 types of viral AU were characterized by unilateral involvement (80%-97%). Rubella virus AU was characterized by younger age at onset and chronic course and typically was associated with cataract at presentation. Heterochromia was present in 23% of RV AU patients. Anterior uveitis associated with HSV or VZV occurred characteristically in older patients and frequently followed an acute course. Clinical features associated with herpetic AU included conjunctival redness, corneal edema, history of keratitis, and development of posterior synechiae. Herpes simplex virus AU often had severe anterior chamber inflammation, whereas the presence of vitritis was more common in RV AU and VZV AU. The prevalence of documented intraocular pressure (IOP) of more than 30 mmHg (25%-50%; P = 0.06) and development of glaucoma (18%-30%; P = 0.686) were similar in all 3 groups. Focal chorioretinal scars were seen in 22% of RV AU eyes, in 0% of HSV AU eyes, and in 11% of VZV AU eyes (P = 0.003). Visual prognosis was favorable for all 3 groups. CONCLUSIONS: These observations identify clinical differences between RV AU, HSV AU, and VZV AU and may be of particular value to ophthalmologists who are unable to carry out intraocular fluid analysis to discriminate between these types of viral AU. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Aquaporin expression in blood-retinal barrier cells during experimental autoimmune uveitis.

PURPOSE: Blood-retinal barrier (BRB) breakdown and retinal edema are major complications of autoimmune uveitis and could be related to deregulation of aquaporin (AQP) expression. We have therefore evaluated the expression of AQP1 and AQP4 on BRB cells during experimental autoimmune uveitis (EAU) in mice. METHODS: C57Bl6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-16. The disease was graded clinically, and double immunolabeling using glial fibrillary acidic protein (GFAP; a marker of disease activity) and AQP1 or AQP4 antibodies was performed at day 28. AQP1 expression was also investigated in mouse retinal pigment epithelium (RPE) cells (B6-RPE07 cell line) by reverse transcriptase PCR and western blot under basal and tumor necrosis factor alpha (TNF-alpha)-stimulated conditions. RESULTS: In both normal and EAU retina, AQP1 and AQP4 expression were restricted to the photoreceptor layer and to the Müller cells, respectively. Retinal endothelial cells never expressed AQP1. In vasculitis and intraretinal inflammatory infiltrates, decreased AQP1 expression was observed due to the loss of photoreceptors and the characteristic radial labeling of AQP4 was lost. On the other hand, no AQP4 expression was detected in RPE cells. AQP1 was strongly expressed by choroidal endothelial cells, rendering difficult the evaluation of AQP1 expression by RPE cells in vivo. No major differences were found between EAU and controls at this level. Interestingly, B6-RPE07 cells expressed AQP1 in vitro, and TNF-alpha downregulated AQP1 protein expression in those cells. CONCLUSIONS: Changes in retinal expression of AQP1 and AQP4 during EAU were primarily due to inflammatory lesions, contrasting with major modulation of AQP expression in BRB detected in other models of BRB breakdown. However, our data showed that TNF-alpha treatment strongly modulates AQP1 expression in B6-RPE07 cells in vitro.

ACUTE FROSTED RETINAL PERIPHLEBITIS IN A PATIENT WITH MEDITERRANEAN FEVER.

PURPOSE: To present a case of frosted branch periphlebitis in a young Armenian patient with familial Mediterranean fever. METHODS: Case report. RESULTS: A 37-year-old man presented with a unilateral decreased visual acuity and floaters for 4 days on the left eye (LE). Visual acuity was 20/20 in the right eye (RE) and 20/28 in the LE. Anterior segment and fundus examinations of the RE were normal. Slit-lamp examination of LE revealed a mild nongranulomatous anterior uveitis and vitritis. Intraocular pressure was 19 mmHg in the RE and 12 mmHg in the LE. Fundoscopy of the LE showed typical appearance of frosted branch periphlebitis with perivascular sheathing of the retinal veins and scattered retinal hemorrhages. Fluorescein angiography of the RE was normal. The LE showed optic disk and segmented vascular staining without macular leakage. Optical coherence tomography of the RE was normal; LE demonstrated a localized macular thickening and few intraretinal cysts. The detailed ophthalmologic history was negative. The general history and workup were significant for familial Mediterranean fever and a positive lupus anticoagulant. One week later, the fundus findings worsened with a severe decrease of visual acuity of the LE to 20/200. A single intravitreal (IVT) injection of bevacizumab was performed. Three weeks after injection, fundus findings progressively improved with a decrease of the macular thickening and an improvement of the visual acuity to 20/25. Clinical improvement continued up to the last visit (19 weeks after the injection) with a visual acuity that reached back 20/20 with no signs of active inflammation. CONCLUSION: This case demonstrates a possible association between unilateral frosted branch periphlebitis and familial Mediterranean fever.

The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings.

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.

Clinical Features of CMV-Associated Anterior Uveitis.

Cytomegalovirus (CMV) anterior uveitis is the most common ocular manifestation of CMV disease in immunocompetent individuals. It is thought to be due to a local reactivation of latent CMV and is usually unilateral. The acute form presents as Posner-Schlossman Syndrome, a recurrent hypertensive anterior uveitis with few granulomatous keratic precipitates. There are geographic differences in the chronic form of CMV anterior uveitis. Asian patients commonly present as Fuchs Uveitis Syndrome with diffuse stellate keratic precipitates, while the European patients present with a chronic hypertensive anterior uveitis with fewer keratic precipitates that are brown in color and located inferiorly. Characteristic features of CMV anterior uveitis include mild anterior chamber inflammation, elevated intraocular pressure, stromal iris atrophy. Synechiae, macular edema and retinitis are typically absent. CMV disease may also be associated with the development of corneal endotheliitis with a reduced endothelial cell count. Long-term complications include glaucomatous optic neuropathy and cataract formation.

Differential Diagnosis of Viral-Induced Anterior Uveitis.

Diagnosis of uveitis is often challenging, but can be easy in typical viral-induced anterior uveitis (VIAU). Associated symptoms and signs are an important source of information. Certain classical clinical features such as keratic precipitates (KPs) distribution, iris atrophy, elevated intraocular pressure (IOP), and unilaterality are commonly used to support the diagnosis of VIAU. However, many etiologies of anterior uveitis may to a certain extent mimic VIAU, especially the ones with unilateral granulomatous KPs and elevated IOP. This review begins with how the clinician can differentiate viral from nonviral anterior uveitis, and subsequently focuses on the key features which may aid in differentiating among the different viruses that cause VIAU.

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers.

PURPOSE: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe. METHODS: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV. RESULTS: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case. CONCLUSION: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.

Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious Uveitis.

PURPOSE: To investigate the effect of a single intravitreal dexamethasone implant (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and intraocular pressure (IOP) in active noninfectious uveitis. METHODS: Medical records of patients with noninfectious active uveitis treated by IVT-DIs were retrospectively reviewed. Uveitis etiologies, treatment indications, best corrected visual acuity (BCVA), central retinal thickness measured by ocular coherence tomography, IOP, and systemic, local, and topical treatments were collected. Parameters were analyzed before the injection of the implant, after 1.5 ± 0.8 months and 4.4 ± 0.9 months for the BCVA, after 2 ± 1.3 months and 4.6 ± 1.3 months for the ocular coherence tomography, and after 1.3 ± 0.7 months and 4.4 ± 1 months for the IOP. RESULTS: We included 14 patients (20 eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%), choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the injection, mean visual acuity was 0.4 ± 0.5 logMAR (logarithm of the minimum angle of resolution) that improved to 0.3 ± 0.5 logMAR (P = 0.0002) after 1.5 ± 0.8 months and to 0.3 ± 0.5 logMAR (P = 0.005) after 4.4 ± 0.9 months. A statistically significant decrease of macular thickness was observed both at 2 ± 1.3 months and at 4.6 ± 1.3 months after IVT-DI. Mean IOP was 16 ± 5 mmHg before injections, 18 ± 6 mmHg (P = 0.13) at 1.3 ± 0.7 months, and 15 ± 4 mmHg (P = 0.65) at 4.4 ± 1 months. By Kaplan-Meier analysis, we found that after 3.3 months, 17% of the eyes still present a BCVA amelioration ≥0.3 logMAR. CONCLUSIONS: In our patients with active noninfectious uveitis, injection of a first single dexamethasone implant was found to improve visual acuity and decrease macular thickness without significant increase of IOP, although the effect seems limited in time.

Topical Ganciclovir in Cytomegalovirus Anterior Uveitis.

PURPOSE: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus (CMV) anterior uveitis in a tertiary uveitis referral center in Brussels, Belgium. METHODS: A retrospective study of patients with a clinical diagnosis of CMV anterior uveitis/endotheliitis demonstrated by a positive polymerase chain reaction and/or Goldmann-Witmer coefficient (GWc). RESULTS: We report a series of 15 patients presenting clinical characteristics of CMV anterior uveitis. Patients had a pretreatment follow-up of 13.00 ± 12.78 months and a posttreatment follow-up of 42.64 ± 31.23 months. The 14 non-Asian patients (93.3%) had clinical characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%) had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation, uveitis was unilateral in all patients, visual acuity (VA) was 0.91 ± 0.25, and all patients had an increased intraocular pressure (IOP), with a mean IOP of 41.40 ± 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had glaucoma, 2 needed glaucoma surgery (13.3%). The mean final VA was 0.93 ± 0.11; 13 patients (86.5%) reached a final VA of 0.7 to 1. Patients had a significantly lower number of recurrences/year posttreatment (0.76 ± 0.57) than in the pretreatment period (3.76 ± 2.44) (P = 0.001). The mean time to recurrence increased from 4.03 months before treatment to 12.58 months after treatment (P = 0.003). CONCLUSION: Our results suggest that patients treated with 0.15% topical ganciclovir have a decreased frequency of CMV anterior uveitis recurrences, most preserve a relatively good central vision over time. However, glaucoma is a frequent and severe complication.

Intraocular T-cell Lymphoma: Clinical Presentation, Diagnosis, Treatment, and Outcome.

PURPOSE: To report on the clinical data of seven patients with T-cell intraocular lymphoma (IOL). METHODS: Retrospective case series. RESULTS: Seven immunocompetent patients, 12 eyes, 6 women, with T-cell-IOL were included from five countries. Mean age was 53.5 years (range: 25-82). Four patients had systemic-ocular lymphoma, two had CNS-ocular lymphoma, and one had systemic-CNS- ocular lymphoma. Vitritis was the most frequent clinical sign, followed by anterior uveitis and serous retinal detachment. Cytopathologic examination was performed on all ocular specimens (vitreous in six and iris mass biopsy in one patient). Adjunctive diagnostic procedures included immunohistochemistry, molecular tests, and cytokine profiling of vitreous samples. Treatment modalities included systemic chemotherapy (five patients), intravitreal methotrexate (three patients), globe radiotherapy, and intrathecal chemotherapy. Mean survival from diagnosis was 21.7 months (range: 2-69). Two patients are still alive. CONCLUSIONS: T-cell IOL has variable clinical manifestations and prognosis. Systemic involvement, SRD, and vitreoretinal involvement were frequently observed.