The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.

Prognostic factors of cataract surgery in patients with uveitis.

PURPOSE: To evaluate the long-term visual outcomes of patients with uveitis undergoing cataract surgery and to identify possible factors influencing the visual prognosis and the development of postoperative complications. METHODS: Retrospective study of all patients with uveitis who underwent cataract surgery between January 2015 and February 2020 in our tertiary referral center. RESULTS: A total of 78 eyes from 78 patients were included in the study. The best-corrected visual acuity (BCVA) improved in 86% of patients, and a BCVA of 0.5 or better was achieved in 57 (73%) patients. A significant correlation was shown between the preoperative and postoperative BCVA (Spearman r = 0.521, p < 0.01). Final BCVA differed between diverse anatomical uveitis entities (p = 0.047), and anterior uveitis demonstrated the best outcomes. Chronic uveitis resulted in a worse final BCVA than acute recurrent uveitis (p = 0.001). The presence of CME any time before the surgery and intermediate uveitis were associated with worse visual prognosis, while systemic therapy for uveitis before surgery and iris manipulation during surgery were not related to visual outcomes. Postoperative development of cystoid macular edema (CME) was closely associated with preexisting CME (p < 0.001) and intermediate uveitis (p = 0.01). CONCLUSIONS: Visual results of cataract surgery in patients with uveitis were beneficial, but limited visual outcomes were more frequently observed in patients with chronic uveitis and intermediate uveitis with a history of CME. In consequence, prevention, or adequate treatment of CME, especially in patients with intermediate uveitis, might result in better visual results of their cataract surgery.

CAUSES AND CLINICAL MANIFESTATIONS OF MASQUERADE SYNDROMES IN INTRAOCULAR INFLAMMATORY DISEASES.

OBJECTIVE: To identify the clinical characteristics and prevalence of neoplastic and nonneoplastic inflammatory masquerade syndromes (IMSs) in a tertiary center and determine the useful diagnostic tests. METHODS: A retrospective cohort study of consecutive 1906 patients diagnosed with intraocular inflammatory disease. RESULTS: Of all patients initially diagnosed with intraocular inflammatory disease, we identified 116 (6%) patients with noninflammatory causes (neoplastic IMSs in 36/116; 31% and nonneoplastic IMSs in 52/116; 45%). In addition, 26 patients (22%, 1.4% of all) had drug-induced uveitis and 2 (2%, 0.1% of all) had paraneoplastic uveitis. The large B-cell lymphoma was the most common neoplastic IMS (78%), and the major clinical features were presence of cells and floaters in the vitreous (69%) and chorioretinal lesions (33%). The causes of nonneoplastic IMSs included retinal vascular disorders (38%), hereditary retinal diseases (31%), and degenerative ocular disorders (19%). The common clinical manifestations consisted of chorioretinal scars (27%), small white-yellow retinal lesions (17%), and leaking vessels on fluorescein angiography (14%). CONCLUSION: Noninflammatory causes were determined in 6% of a large population with initial diagnosis of intraocular inflammatory disease. Although neoplastic IMS was commonly characterized by vitreous cells and opacities, most common definitive diagnoses in nonneoplastic IMS encompassed diverse retinal disorders.

Relevance of erythrocyte sedimentation rate and C-reactive protein in patients with active uveitis.

PURPOSE: To relate erythrocyte sedimentation rates (ESR) and C-reactive protein (CRP) values to different uveitis entisties. METHODS: A retrospective study of patients with a first episode of active uveitis visiting the Erasmus University Medical Center, uveitis clinic, Rotterdam, the Netherlands, was performed. Levels of ESR and CRP were determined within 2 weeks and 1 week after onset of uveitis, respectively. Uveitis had to be of unknown origin at that moment. The specific etiologic groups were related to ESR and CRP values. RESULTS: The majority of patients with uveitis had ESR and/or CRP values within the normal limits and no association of ESR and/or CRP with the specific cause of uveitis was observed. However, elevation of ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L was mostly seen in patients with systemic immune-mediated diseases (8/59, 14% of all with immune-mediated diseases) or systemic infectious causes (7/38, 18% of all infectious uveitis). Patients with ocular toxoplasmosis typically exhibited normal ESR and CRP (9/11, 82%) while patients with endogenous endophthalmitis had elevated ESR and/or CRP in 6/7, 86%. Sarcoidosis-associated uveitis showed predominantly elevated ESR (13/24, 54%; range 20-59 mm/h in 11/13, 85%). Human immunodeficiency virus-positive patients had more often elevated ESR values when compared to the remainder of patients (9/11, 82% vs. 64/163, 39%, 18%, P = 0.009). The cause of uveitis was established in 19/20 (95%) of patients with ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L. CONCLUSIONS: The majority of patients with first attack of uveitis had ESR and CRP within the normal limits. Elevated levels of ESR and CRP reflected systemic involvement and high levels of both values were associated with established uveitis cause.

Efficacy of glaucoma drainage devices in uveitic glaucoma and a meta-analysis of the literature.

PURPOSE: To assess the efficacy of glaucoma drainage devices (GDD) in uveitic glaucoma and non-uveitic glaucoma, and to perform a meta-analysis of previously published results to compare with our data. METHODS: Retrospective case-control study, in which all eyes that underwent GDD surgery were included from 2015 onwards. Cases were defined as patients with uveitic glaucoma. Patients with non-uveitic glaucoma served as controls. To compare our results, a review of the literature was performed using PubMed database. RESULTS: A total of 99 eyes were included (38 with uveitic glaucoma). The preoperative IOP was 25.9 ± 7.7 mmHg and 27.9 ± 9.6 mmHg for patients with and without uveitis (p = 0.277). No significant differences were found between patients with and without uveitis in the final IOP or reduction in IOP (44.9% vs. 42.8%, respectively). Within the first year after surgery, 13.2% of cases developed macular edema (vs. 6.6%; p = 0.267) and 15.8% a transient hypotony (vs. 8.2%; p = 0.242). A meta-analysis of 24 studies showed a postoperative weighted mean difference of - 17.8 mmHg and 2.2 lower number of IOP-lowering medications in uveitic glaucoma (compared to - 13.2 mmHg and 3.5 in the current study, respectively). CONCLUSION: GDD surgery in patients with uveitis has a similar effect on IOP as in patients without uveitis. The risks of developing macular edema and hypotony were slightly higher in patients with uveitis, but the results were not statistically significant. These findings are in line with previous reports, though data on the efficacy of GDD surgery and macular edema in uveitic glaucoma is scarce.

ADALIMUMAB THERAPY FOR REFRACTORY BIRDSHOT CHORIORETINOPATHY.

PURPOSE: To report the outcome of using adalimumab to treat birdshot chorioretinopathy. METHODS: Retrospective case series of 19 patients (38 eyes) with HLA-A29-positive birdshot chorioretinopathy who received adalimumab treatment. Patients had been refractory to previous standard systemic immunomodulatory therapy. They received biweekly subcutaneous injections of 40 mg of adalimumab. Outcome measures were change in visual acuity, fluorescein angiography, and optical coherence tomography features, the concomitant use of immunosuppressive drugs, and the occurrence of adverse effects between 1 year before, at baseline, and after 1 year of adalimumab treatment. RESULTS: Mean Snellen visual acuity at 1-year follow-up was 20/28, an improvement from 20/43 at the start of the treatment (P = 0.011) and equal to the visual acuity 1 year before the treatment (20/29). Only 2 of the 9 patients who had complete fluorescein angiography and optical coherence tomography results after the 1 year of treatment were completely free of inflammation signs at the end of the follow-up. Half (53%) of 17 patients were receiving adalimumab monotherapy after 1 year of treatment, an increase from 21% at the start of treatment (P = 0.047). Three of the 19 patients reported possible side effects; 2 discontinued treatment within 1 year. CONCLUSION: The results suggest that adalimumab is effective at improving visual acuity and at tapering concomitant immunomodulatory therapy, in patients with refractory birdshot chorioretinopathy. However, complete remission is rarely achieved.

Autoantibody profiling in intraocular fluid of patients with uveitis.

A high prevalence of serum antiretinal antibodies (ARAs) in patients with uveitis has been previously described, though their clinical role remains elusive. Assessment of intraocular ARAs may provide further insight into the pathogenesis of diverse uveitis entities. In this study we investigate the prevalence of multiple specific anti-ocular antibodies (AOcAs), including ARAs, in intraocular fluid of patients with uveitis. Autoantibody profiling with 188 different ocular antigens was performed by a multiplex immunoassay with intraocular fluid samples of 76 patients with uveitis. Clinical data from uveitis patients were collected and statistical analyses were executed to evaluate associations between intraocular AOcAs and clinical characteristics. Controls consisted of 19 intraocular fluid samples from cataract patients. A spectrum of 22 different AOcAs was present in higher levels in patients with uveitis than in controls (p < 0.05), but in moderately elevated titers (<2x). High elevations of intraocular AOcAs in uveitis (>5x compared to cataract) were observed in varicella zoster virus-induced uveitis, multiple sclerosis-associated uveitis and patients with unexplained uveitis but positive quantiferon test. Presence of macular edema was associated with increased intraocular levels of tyrosinase antibodies. Our results show that patients with uveitis are characterized by the presence of a broad spectrum of moderately elevated levels of intraocular AOcAs, and high intraocular AOcA levels were found in several specific uveitis entities. This study favors secondary production of AOcAs and not their inciting role.

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.

Focal chorioretinitis in Thailand.

PURPOSE: To report the clinical features of patients with focal chorioretinitis (FCR), as well as toxoplasma serology. METHODS: We included 25 (4%) consecutive patients with FCR of 593 with uveitis. Controls consisted of 127 patients with posterior and panuveitis and clinical features other than FCR. Results of enzyme-linked immunosorbent assay for anti-Toxoplasma gondii immunoglobulin G (IgG) and IgM, demographic data, and clinical features of patients were registered. RESULTS: Positive anti-T. gondii IgG levels were observed in 21 of 25 patients (84%) with FCR in contrast to 14 of 127 patients (11%) with non-FCR (P < 0.001, Fisher test). The IgG levels >600 IU were found in 19 of 25 patients (76%) with FCR and in none of the patients with non-FCR (P < 0.001). All cases had unilateral involvement. Ocular features consisting of FCR and vitritis were present in all patients, but associated chorioretinal atrophic scars were not commonly seen (7/25 eyes; 28%). Retinal vasculitis was found in 9 of 25 eyes (36%) and affected solely the arteries. CONCLUSION: The majority of patients with FCR in Thailand exhibit highly positive anti-T. gondii IgG levels suggesting the presence of active systemic infection, which is also consistent with the absence of old scars. The absence of old scars and retinal arteritis were the features distinct from typical ocular toxoplasmosis lesions reported in the European and the U.S. series.

Diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of unknown cause.

PURPOSE: To compare the yield of diagnostic pars plana vitrectomy (PPV) with the yield of aqueous analyses in patients with uveitis of unknown cause. METHODS: Seventy-five consecutive patients (84 eyes) with uveitis involving posterior eye segment who undergo a diagnostic PPV from 2005 through 2009 were retrospectively reviewed. Vitreous specimens were simultaneously analyzed by microbiological culture, flow cytometry, and cytology as well as by polymerase chain reaction and for intraocular antibody production by Goldmann-Witmer coefficient. In 53 eyes, both aqueous and vitreous samples were assessed. The primary outcome measure was the comparison between vitreous and aqueous analyses. RESULTS: Vitreous analysis was positive in 18 of 84 eyes (21%). Positive results indicated infectious uveitis in 12 of 18 cases (67%) and lymphoma in 6 of 18 (33%) cases. Of the 53 eyes with both aqueous and vitreous samples available, aqueous analysis revealed the diagnosis in 6 of 53 eyes and vitreous in 9 of 53 eyes. Unilateral uveitis (P = 0.022), panuveitis and uveitis posterior (P ≤ 0.001), preoperative immunosuppressive therapy (P = 0.004), and increasing age (P = 0.018) were associated with an increased diagnostic yield of PPV. Overall, 1 year after PPV, median visual acuity improved from 20/200 to 20/80 (Snellen, P ≤ 0.001). Of 18 patients who were on immunosuppressive treatment before PPV, 8 (44%) were able to stop immunosuppressive therapy during 1-year follow-up. The complications of PPV consisted predominantly of cataract development (33/65, 51%). CONCLUSION: Diagnostic PPV with the analysis of vitreous fluid by multiple laboratories for infectious and malignant disorders was useful in diagnosing uveitis of unknown cause. Previous aqueous analysis was especially valuable for the diagnosis of intraocular infections and may therefore decrease the number of patients who would otherwise undergo an invasive diagnostic PPV. Furthermore, PPV was associated with improved visual acuity and decreased use of immunosuppressive therapy.

The Presence of Pigmentation on Central Anterior Lens Capsule in the Human Leukocyte Antigen B27-Associated Anterior Uveitis and Its Value in Clinical Diagnosis.

PURPOSE: To report on the value of presence of pigmentation on central anterior lens capsule (PioLe) in HLA B27- associated anterior uveitis (HLA B27-AU). METHODS: 268 patients (320 eyes) with AU were reviewed. Two diagnostic models to predict probability of HLA-B27-AU were developed. The first model included 6 variables (age, gender, unilaterality, presence of non-granulomatous keratic precipitates, hypopyon, and intraocular pressure (IOP). The second model was developed to investigate the added value of PioLe into the first model. RESULTS:      Unilaterality, presence of hypopyon, IOP <21 mmHg and PioLe were characteristic for HLA-B27 positive patients (P≤0.003 for all). All of 6 variables had area under receiver operating characteristic curves (AuROC) ≤ 60, but PioLe reached even higher value (65.5). Diagnostic model I and II had AuROC 76.3% (95%CI, 68.4%-84.2%) and 80.0% (95%CI, 72.6%-87.5%), respectively. CONCLUSIONS: Unilaterality, hypopyon, IOP <21 mmHg and presence of PioLe are clinical signs suggesting HLA B27- AU.

Interleukin-17 production and T helper 17 cells in peripheral blood mononuclear cells in response to ocular lysate in patients with birdshot chorioretinopathy.

PURPOSE: To determine the cytokine response to ocular lysates of peripheral blood mononuclear cells (PBMCs) from patients with birdshot chorioretinopathy (BSCR). METHODS: In the PBMCs of 19 patients with BSCR, T cell cytokine production in response to human retina and choroid lysates was analyzed with flow cytometry and compared to the responses against skin lysates. Five patients had active disease and had not yet been treated (naïve to systemic therapy); 14 patients had either immunomodulatory therapy (IMT) or inactive disease (referred as inactive/IMT). The PBMCs of 11 HLA-A29-positive healthy individuals were used as controls. RESULTS: The levels of interleukin-17 (IL-17) in supernatant of cultures stimulated with retina lysate were higher in patients with active BSCR compared to the HLA-A29 positive controls. The levels of other T cell cytokines (IL-10 and interferon-γ [IFN-γ]) in PBMC cultures did not change significantly after stimulation with ocular lysate. The frequency of CD4(+) IL-17(+) (T helper 17 [Th17]) T cells but not of CD4(+) IFN-γ (Th1) T cells was elevated in the PBMCs of patients with active BSCR stimulated by retina lysates compared to skin lysates. CONCLUSIONS: Our data demonstrate that PBMCs exhibit an IL-17-mediated immune response to retina lysate in patients with active disease naïve to systemic therapy. This is accompanied by the enrichment of IL-17-producing CD4(+) T cells. These findings support the current concept of chronic Th17-cell mediated inflammation and provide evidence that links the Th17 signatures to ocular-specific immune responses in BSCR.

Clinical and Microbiological Manifestations of Endogenous Endophthalmitis in Tertiary Care Hospital, Northern Thailand.

PURPOSE: To determine the characteristics, primary sources, pathogens, risk factors, and visual outcomes in patients with endogenous endophthalmitis (EE). METHODS: We performed a retrospective cohort study of 61 consecutive patients with EE (74 affected eyes) and reported on prevalence, clinical courses, prognostic factors and visual outcomes. RESULTS: Prevalence of EE was 5% of all patients with endophthalmitis. Among culture-positive cases (89%), Gram-positive species dominating (69%) followed by Gram-negative with 22% and fungal species with 9%. Regarding to visual outcomes, the mean visual acuity (VA, ETDRS letters) at baseline, 3-months, 6-months and 1-year follow-up was 0.85, 9, 8 and 9, respectively. Initial VA of hand movement or better (P 0.007) and bilateral infection (P 0.004) were associated with better visual outcome. CONCLUSION: The prognosis for EE remained poor despite aggressive and immediate treatment. The high suspicion, early diagnosis and prompt treatment are important factors that might lead to the better outcome.

Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.

Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.

Evaluation of pre-processing methods for tear fluid proteomics using proximity extension assays.

Tear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the analysis and between-study comparisons. We studied two different pre-processing methods, specifically the use of punches of the strip versus elution of the strip in a buffer. Tear fluid filled Schirmer strips were collected from 5 healthy participants, and divided into two halves over the length of the strip. In either part, punches or eluates were obtained from 4 different locations, from the first part touching the eye (head) to the end, to assess the protein distribution along the strips. The levels of 92 inflammatory proteins were measured in the punches/eluates using proximity extension assays. The punch method yielded higher protein detectability compared to the elution method (76% vs 66%; p ≤ 0.001). Protein expression level was found to be slightly higher in the head of the strip, however, 3 out of 5 punches from the head failed quality control. Protein expression levels over the remaining parts of the strips were similar. Our study showed beneficial use of punches of any part of the strip except the head in future biomarker research.

Cytokines in tear fluid of patients with ocular graft-versus-host disease after allogeneic stem cell transplantation.

PURPOSE: To investigate the profile of cytokines in tear fluid of patients after allogeneic stem cell transplantation (allo-SCT) and determine their relation to the presence and manifestations of ocular graft-versus-host disease (GvHD). METHODS: In this cross sectional study tear fluid was collected in 34 consecutive adult patients that previously underwent allo-SCT (16 with ocular GvHD and 18 without) and 16 age- and gender-matched healthy controls using the Schirmer test under local anesthesia. Tear fluid was analyzed by multiplex immunoassay for the presence of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Levels of measured cytokines were correlated with the findings in slit lamp examination and the Ocular Surface Disease Index (OSDI). RESULTS: The levels of IL-6 and IFN-γ in tear fluid in ocular GvHD patients were significantly elevated in comparison to patients without ocular GvHD and healthy controls (p<0.005 for each) The levels of IFN-γ correlated with the Schirmer score (r=-0.48, p<0.0001) and tear break up time (TBUT; r=-0.38, p=0.03). Tear IL-6 levels correlated with complaints of dry eyes (r=0.39, p=0.02), tear production (r=-0.59, p<0.0001), fluorescent staining of the cornea (r=0.42, p=0.01), and with the OSDI score (r=0.40, p=0.005). CONCLUSIONS: IL-6 and IFN-γ were elevated in tear fluid of patients with ocular GvHD and correlated with different symptoms of dry eye disease, suggesting that IFN-γ is elevated during the early stages and IL-6 is involved in later stages of ocular GVHD and exhibits moreover an association with its severity.

Clinical manifestations of human immunodeficiency virus-induced uveitis.

PURPOSE: To describe the clinical manifestations of patients with human immunodeficiency virus (HIV)-induced uveitis in Thailand. DESIGN: Prospective cohort study of 6 patients with HIV-induced uveitis. PARTICIPANTS: Six patients (8 eyes) with HIV-induced uveitis who had an extremely high intraocular: plasma HIV-1 RNA ratio. METHODS: The clinical manifestations and laboratory findings are reported of 6 consecutive patients with HIV-induced uveitis who had an extremely high intraocular-to-plasma HIV-1 RNA ratio and were diagnosed between July 2009 and May 2011. MAIN OUTCOME MEASURES: Clinical manifestations and laboratory findings. RESULTS: Human immunodeficiency virus-induced uveitis was diagnosed in 4 men and 2 women with an average age of 41 years at presentation. None of the patients were receiving highly active anti-retroviral therapy (HAART) or had clinical or laboratory evidence, or both, of opportunistic infections. The mean plasma load was 218 688 copies/ml (median, 137 500 copies/ml; range, 24 900-540 000 copies/ml), and the mean intraocular HIV load was 20 937 755 copies/ml (median, 7 499 000 copies/ml; range, 2 460 000-89 800 000 copies/ml). The average CD4 cell count was 192 cells/µl (median, 248 cells/µl; range, 5-342 cells/µl). All the patients had decreased vision, and none had conjunctival hyperemia. The anatomic location of uveitis was anterior in all patients, and associated vitreitis was present in 4 patients; none exhibited retinal lesions or scars. Anterior segment inflammation and keratic precipitates were observed in all patients, and none responded to topical corticosteroid therapy. After the administration of HAART, the intraocular inflammation disappeared entirely within several weeks in all of the patients and the intraocular and plasma HIV loads decreased. CONCLUSIONS: Human immunodeficiency virus-induced uveitis should be suspected in HAART-naïve, HIV-positive patients or in those in whom this treatment fails and who have anterior uveitis without any retinal lesions and exhibit no response to topical corticosteroids. The concurrent determination of HIV load in the intraocular fluids and plasma may clarify the cause of HIV-associated uveitis.

Idiopathic Epiretinal Membranes: Visual Outcomes and Prognostic Factors

Objectives: To evaluate the associations between anatomical changes and visual outcomes in patients with idiopathic epiretinal membrane (ERM). Materials and Methods: We performed a prospective study of 130 consecutive idiopathic ERM patients and report their visual outcomes and the factors associated with visual outcome and anatomical changes. Results: Of 130 eyes of 130 patients, 87 eyes underwent surgery, while the remaining 43 eyes were observed. At 6-month follow-up, the best-corrected visual acuity (BCVA) increased in the whole population. Mean Early Treatment Diabetic Retinopathy Study letter score changed from 51 to 65 in the surgical group and from 67 to 68 in the non-surgical group. The surgical group had improvement in BCVA at all ERM stages and grades of disorganization of the retinal inner layers (DRIL) (p<0.01). In multivariable analysis of the surgical group, factors associated with BCVA of ETDRS 60 letters or more were no or mild DRIL and the absence of ellipsoid zone disruption at baseline (p=0.002 and p=0.034, respectively) and this statistically significant positive correlation was still maintained at 12-month follow-up. Conclusion: Baseline DRIL grade and presence of ellipsoid zone disruption were the most informative prognostic factors in patients with idiopathic ERMs. Patients with severe DRIL and/or advanced ERMs had improved vision after ERM removal.