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Purpose: Analyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP)., Design: Retrospective multicenter study., Participants: Patients with OMMP seen at the Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990 to 2022., Methods: Data at presentation on demographics, direct immunofluorescence, ocular findings, sites of extraocular manifestations (EOMs), and previous treatments in patients with a clinical or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes., Main Outcome Measures: (1) Inflammatory control (no conjunctival inflammation in both eyes at 3 months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥ 1 cicatrizing stage progression in either eye); and (4) vision loss (≥ 2 Snellen lines)., Results: A total of 117 patients (234 eyes), 61% (71/117) of whom were women, with a mean age of 66.6 (SD: 12.4) years (range: 37-97 years) and median follow-up of 34 months (interquartile range: 16-66 months; range: 3-265 months), were enrolled. Inflammatory control was achieved in 57% of patients (67/117), with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital involvement (adjusted odds ratio [aOR]: 12.51; 95% confidence interval [CI]: 2.61-59.99; P = 0.002) and corneal scarring (aOR: 3.06; 95% CI, 1.15-8.14; P = 0.025), as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% of patients (23/117), 12% of patients (14/117), and 27% of patients (32/117), respectively. Baseline corneal scarring was a risk factor for relapse (adjusted hazard ratio: 4.14; 95% CI: 1.61-10.62; P = 0.003), progression (aOR: 11.46; 95% CI: 1.78-73.75; P = 0.010), and vision loss (aOR: 3.51; 95% CI: 1.35-9.10; P = 0.010). HR-EOM was associated with stage progression (aOR, 34.57; 95% CI, 6.57-181.89; P<0.001) and vision loss (aOR, 8.42; 95% CI, 2.50-28.42; P = 0.001). No significant differences were found between IMT regimes and relapse (P = 0.169)., Conclusions: Ocular mucous membrane pemphigoid presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation., Design: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil., Participants: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft., Methods: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks., Main Outcome Measure: The 52-week endothelial immune rejection rate., Results: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis., Conclusions: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to identify the genetic cause of a new multiple congenital anomalies syndrome observed in three individuals from two unrelated families., Methods: Clinical assessment was conducted prenatally and at different postnatal stages. Genetic studies included exome sequencing (ES) combined with single-nucleotide polymorphism (SNP) array based homozygosity mapping and trio ES. Dermal fibroblasts were used for functional assays., Results: A clinically recognizable syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet was identified. Additional features included eye abnormalities, hearing impairment, and electroencephalogram anomalies. ES detected different homozygous truncating variants in MAPKAPK5 in both families. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization., Conclusion: Our data indicate that loss-of-function variants in MAPKAPK5 result in a severe developmental disorder and reveal a major role of this gene in human brain, heart, and limb development.

Purpose: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy., Design: Multicenter, randomized, double-masked, vehicle-controlled trial., Participants: Patients with neurotrophic persistent epithelial defect with or without stromal thinning., Methods: The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat., Main Outcome Measures: The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8., Results: Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient., Conclusions: Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism., Methods: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing., Results: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM&#95;006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders., Conclusion: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.

Purpose: To determine the impact of total pars plana vitrectomies (PPVs) with peripheral shaving of the vitreous base on the rates of postoperative complications in patients with aphakic, snap-on type I Boston keratoprostheses (KPros)., Design: Retrospective, consecutive case series., Participants: A total of 48 eyes in 46 patients with implantation of aphakic, snap-on type 1 Boston KPros performed at a tertiary care facility between January 1, 2007, and December 31, 2013, were included., Methods: The cumulative incidences of postoperative complications were compared between patients who underwent total PPVs with shaving of the vitreous base (n = 22) and those who had partial PPVs or anterior vitrectomies (AVs) at the time of KPro implantation (n = 26)., Main Outcome Measures: Rates of complications between patients who underwent total PPVs and partial PPVs or AVs., Results: The rate of total postoperative complications was lower in the total PPV group (P = 0.018, log-rank test). In particular, eyes that underwent total PPVs had lower rates of retroprosthetic membranes (RPMs) requiring intervention (P = 0.049) and less vision loss due to glaucoma progression (P = 0.046). There was also a trend for fewer corneal melts (P = 0.060) and less sight-threatening complications (P = 0.051) in the total vitrectomy group. There was no difference in the rates of KPro extrusion (P = 0.41), endophthalmitis or vitritis (P = 0.15), retinal detachments (P = 0.76), cystoid macular edema (P = 0.83), or timing of complications between the 2 groups. The mean preoperative and postoperative visual acuities were similar between the 2 groups (P = 0.97). The mean follow-up was 49±22 months., Conclusions: Eyes that underwent total PPVs during implantation of aphakic, snap-on, type I Boston KPros had less postoperative complications than eyes with partial PPVs or AVs during the average 4 years of follow-up., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the use of Bowman's layer (BL) vertical topographic thickness maps in diagnosing keratoconus (KC)., Design: Prospective, case control, interventional case series., Participants: A total of 42 eyes: 22 eyes of 15 normal subjects and 20 eyes of 15 patients with KC., Intervention: Bowman's layer 2-dimensional 9-mm vertical topographic thickness maps were created using custom-made ultra high-resolution optical coherence tomography., Main Outcome Measures: Bowman's layer average and minimum thicknesses of the inferior half of the cornea, Bowman's ectasia index (BEI; defined as BL minimum thickness of the inferior half of the cornea divided by BL average thickness of the superior half of the cornea multiplied by 100), BEI-Max (defined as BL minimum thickness of the inferior half of the cornea divided by BL maximum thickness of the superior half of the cornea multiplied by 100), keratometric astigmatism (Ast-K) of patients with KC, and average keratometric (Avg-K) readings., Results: In patients with KC, BL vertical thickness maps disclosed localized relative inferior thinning of the BL. Inferior BL average thickness (normal = 15±2, KC = 12±3 μm), inferior BL minimum thickness (normal = 13±2, KC = 7±3 μm), BEI (normal = 91±7, KC = 48±14), and BEI-Max (normal = 75±8; KC = 40±13) all showed highly significant differences in KC compared with normal subjects (P< 0.001). Receiver operating characteristic (ROC) curve analysis showed excellent predictive accuracy for BEI and BEI-Max with 100% sensitivity and specificity (area under the curve [AUC] of 1) with cutoff values of 80 and 60, respectively. The AUC of inferior BL average thickness and minimum thickness were 0.87 and 0.96 with a sensitivity of 80% and 93%, respectively, and a specificity of 93% and 93%, respectively. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max correlated highly to Ast-K (R = -0.72, -0.82, -0.84, and -0.82, respectively; P< 0.001) and to Avg-K (R = -0.62, P< 0.001; R = -0.59, P = 0.001; R = -0.60, P< 0.001; and R = -0.59, P = 0.001, respectively)., Conclusions: Bowman's layer vertical topographic thickness maps of patients with KC disclose characteristic localized relative inferior thinning. Inferior BL average thickness, inferior BL minimum thickness, BEI, and BEI-Max are qualitative and quantitative indices for the diagnosis of KC that accurately correlate with the severity of KC. In our pilot study, BEI and BEI-Max showed excellent accuracy, sensitivity, and specificity in the diagnosis of KC., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Keratoplasty is the primary treatment to cure blindness due to corneal opacification. However, immune-mediated rejection remains the leading cause of keratoplasty failure. Here, we utilize an in vivo imaging approach to monitor, track, and characterize in real-time the recruitment of GFP-labeled allo-specific activated (Bonzo) T cells during corneal allograft rejection. We show that the recruitment of effector T cells to the site of transplantation determined the fate of corneal allografts, and that local intra-graft production of CCL5 and CXCL9/10 regulated motility patterns of effector T cells in situ, and correlated with allograft rejection. We also show that different motility patterns associate with distinct in vivo phenotypes (round, elongated, and ruffled) of graft-infiltrating effector T cells with varying proportions during progression of rejection. The ruffled phenotype was characteristic of activated effectors T cells and predominated during ongoing rejection, which associated with significantly increased T cell dynamics within the allografts. Importantly, CCR5/CXCR3 blockade decreased the motility, size, and number of infiltrating T cells and significantly prolonged allograft survival. Our findings indicate that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells, and may guide targeted interventions to promote graft survival., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: To assess the use of ultra-high-resolution (UHR) optical coherence tomography (OCT) in the diagnosis of ocular surface lesions., Design: Prospective, noncomparative, interventional case series., Participants: Fifty-four eyes of 53 consecutive patients with biopsy-proven ocular surface lesions: 8 primary acquired melanosis lesions, 5 amelanotic melanoma lesions, 2 nevi, 19 ocular surface squamous neoplasia lesions, 1 histiocytosis lesion, 6 conjunctival lymphoma lesions, 2 conjunctival amyloidosis lesions, and 11 pterygia lesions., Intervention: Ultra-high-resolution OCT imaging of the ocular surface lesions., Main Outcome Measures: Clinical course and photographs, UHR OCT image, and histopathologic findings., Results: Ultra-high-resolution OCT images of all examined ocular surface lesions showed close correlation with the obtained histopathologic specimens. When clinical differential diagnosis of ocular surface lesions was broad, UHR OCT images provided optical signs indicating a more specific diagnosis and management. In cases of amelanotic melanoma, conjunctival amyloidosis, and primary histiocytosis and in 1 case of ocular surface squamous neoplasia, UHR OCT was instrumental in guiding the diagnosis. In those cases, UHR OCT suggested that the presumed clinical diagnosis was incorrect and favored a diagnosis that later was confirmed by histopathologic examination., Conclusions: Correlations between UHR OCT and histopathologic findings confirm that UHR OCT is an adjunctive diagnostic method that can provide a noninvasive means to help guide diagnosis and management of ocular surface lesions., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report a novel diagnostic technique and a case series of conjunctival and corneal intraepithelial neoplasia (CCIN) diagnosed and followed up using prototype ultra high-resolution (UHR) optical coherence tomography (OCT)., Design: Prospective, noncomparative, interventional case series., Participants: Seven eyes of 7 consecutive patients with CCIN treated using topical interferon alfa-2b or 5-fluorouracil and 7 eyes of 6 consecutive patients with history of surgically excised pterygia., Intervention: Ultra high-resolution OCT imaging of the ocular surface at primary diagnosis of CCIN and during the follow-up period until resolution of the lesion. Ultra high-resolution OCT images of sites of excised pterygia also were captured and compared with images from resolved CCIN patients., Main Outcome Measures: Clinical course and photographs, UHR OCT images, and histopathologic findings., Results: Ultra high-resolution OCT was capable of providing a noninvasive optical biopsy of all examined CCIN lesions. Ultra high-resolution OCT images of the lesions disclosed a thickened hyperreflective epithelium and abrupt transition from normal to hyperreflective epithelium in all 7 cases. Ultra high-resolution OCT images showed excellent correlation with histopathologic specimens obtained at primary diagnosis of the cases that had incisional biopsies before treatment. All patients were treated medically and were followed up for clinical resolution. In 4 patients, at clinical resolution, UHR OCT images also showed normal epithelial configuration at the site of the treated lesions. In 3 patients, despite apparent clinical resolution, the UHR OCT was able to detect residual disease that was clinically invisible. Continuation of treatment resulted in complete resolution of the residual lesions on the UHR OCT images in all cases. Ultra high-resolution OCT images of patients with surgically excised pterygia demonstrated similar findings to resolved CCIN cases., Conclusions: Ultra high-resolution OCT is a novel noninvasive technique to diagnose and manage medically treated CCIN. Using UHR OCT to guide medical treatment could prevent the premature termination of topical treatment in the presence of subclinical disease. A larger sample size is needed for further validation of its sensitivity and specificity., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides-Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome-can present with various ophthalmic manifestations. In a subset of patients, these findings may be the earliest indicators of systemic disease. Orbital and anterior segment findings are most common, whereas posterior segment complications such as retinal vasculitis and optic neuropathy occur much less frequently. This article describes the distinguishing features of associated ophthalmic disease, focusing on the manifestations clinicians are most likely to encounter and those with the most significant ocular morbidity. Although the ANCA-associated vasculitides require systemic workup and treatment, this article discusses diagnostic and therapeutic modalities often used concurrently for ophthalmic disease., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate the capability of ultra-high-resolution (UHR) anterior segment optical coherence tomography (OCT) to image Descemet's membrane (DM) and measure its thickness in vivo. (2) To evaluate the use of DM characteristics and thickness in the diagnosis of Fuchs' dystrophy., Design: Case-control study., Participants: Twenty eyes of 12 Fuchs' dystrophy patients, 20 eyes of 13 young normal, and 20 eyes of 15 elderly normal subjects., Methods: Subjects were imaged using novel, custom-built UHR-OCT. Images were used to describe the characteristics of DM. Custom-made software was used to measure DM thickness and central corneal thickness (CCT). Specimens of DM obtained from Fuchs' dystrophy patients who underwent endothelial keratoplasty (EK) were histopathologically examined. Regression analyses were used to assess the correlation of DM thickness measured by UHR-OCT in vivo and by light microscopy and to determine the intergroup correlations between age, CCT, and DM thickness., Main Outcome Measures: We assessed DM characteristics and thickness, CCT, and age., Results: Using UHR-OCT, the DM seemed in normal young subjects as a single, opaque, smooth line and in normal elderly subjects as a band of 2 smooth opaque lines with a translucent space in between. In Fuchs' dystrophy, DM appeared as a thickened band of 2 opaque lines; the anterior line was smooth whereas the posterior line had a wavy and irregular appearance with areas of localized thickenings. The DM thickness measured in vivo by UHR-OCT correlated significantly with that measured by light microscopy in 5 Fuchs' dystrophy eyes that underwent EK. The average central thicknesses of DM in normal young, in normal elderly and in Fuchs' dystrophy eyes were 10+/-3, 16+/-2, and 34+/-11 microm, respectively (P<0.001). There was a significant correlation between age and DM thickness only in normal groups. In Fuchs' dystrophy patients, there was a significant correlation between CCT and DM thickness that was not significant for normal groups., Conclusions: Ultra-high-resolution OCT is an innovative technique for the in vivo imaging of DM. Determining DM characteristics and thickness by UHR-OCT could be a new approach for the diagnosis of Fuchs' dystrophy., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the rates of adverse ocular events after intravitreal triamcinolone acetonide (IVTA) injection in patients with and without uveitis., Design: Retrospective observational case series., Participants: Two hundred twenty-two eyes of 173 patients were included in the study: 45 eyes of 31 patients with macular edema (ME) due to uveitis and 177 eyes of 142 patients with ME secondary to other etiologies., Methods: Retrospective review of patients who received IVTA at the Cole Eye Institute for ME attributable to various causes between the years 2001 and 2005. Data review of clinical records included patient demographics, etiology of ME, and adverse outcomes after injection. Rates of adverse outcomes in patients with and without uveitis were compared., Main Outcome Measures: Intraocular pressure (IOP) elevation and posterior subcapsular cataract (PSC) progression., Results: Uveitis patients were significantly younger, more likely to be female, and more likely to have had prior posterior sub-Tenon's capsule steroid injection and/or glaucoma therapy than their nonuveitis counterparts. In a multivariate analysis adjusting for the differences in these factors, the presence of uveitis was the strongest risk factor for an adverse IOP event (odds ratio, 2.5; 95% confidence interval [CI], 1.0-6.1; P = 0.05). The odds of having a documented increase in PSC after IVTA injection were 5.6 times greater in uveitis eyes (P = 0.007; 95% CI, 1.6-19.6)., Conclusions: Intraocular pressure elevation and PSC progression occurred with greater frequency in uveitis patients receiving IVTA. Patients with uveitis treated with IVTA should be counseled about these risks and monitored closely.

Purpose: To determine the diagnostic yield of tests commonly used for vitreous fluid analysis in eyes with suspected intraocular infection or malignancy., Design: Noncomparative interventional case series., Participants: Forty-four consecutive patients (45 eyes) treated from 1998 through 2006 with posterior segment inflammation who underwent pars plana vitrectomy for diagnostic purposes., Intervention: Vitreous specimens obtained via pars plana vitrectomy were analyzed by microbiologic culture, cytologic analysis, and flow cytometry., Main Outcome Measures: Diagnostic yield and sensitivity of each test performed on vitreous specimens and visual outcomes of eyes that underwent diagnostic vitrectomy (DVx)., Results: Preoperative diagnoses were infection in 15 eyes and malignancy in 30 eyes. Overall, vitreous analysis identified a specific cause in 9 (20%) of 45 eyes. The overall sensitivity of DVx was 63.6%. The sensitivities of individual tests were: culture, 50%; cytologic analysis, 66.7%; and flow cytometry, 83.3%. The yields of diagnostic tests were: culture, 5.7%; cytologic analysis, 14.3%; and flow cytometry, 20.6%. Final diagnoses were infection in 6 eyes, malignancy in 9 eyes, and idiopathic in 30 eyes. Mean visual acuity improved significantly in the first 6 months after DVx. Visual acuity improved in 60% of eyes, with 37.8% of eyes improving by 3 lines or more., Conclusions: Analysis of vitreous fluid by widely available tests is useful in identifying intraocular infection or malignancy. Most patients experienced a substantial improvement in vision.

Purpose: Anti-tumor necrosis factor alpha (anti-TNF-alpha) agents are being used increasingly in refractory inflammatory eye diseases. We reviewed our patients on etanercept and infliximab to determine whether these medications are equally efficacious in controlling ocular inflammation., Design: Exploratory retrospective analysis., Participants: Patients with ocular inflammatory disease on an anti-TNF-alpha agent (etanercept, infliximab)., Methods: Case records of 22 patients treated with anti-TNF-alpha therapy were reviewed for demographic information, ocular and systemic diagnosis, duration and dose of anti-TNF-alpha treatment, concomitant ocular and systemic immunosuppressive medications, and treatment response., Main Outcome Measures: Uveitis recurrence rate, initial treatment response, treatment response, and medication use at 6 months, 1 year, and last visit., Results: Patients treated with infliximab had a significant decrease in uveitis recurrences after starting therapy compared with those treated with etanercept (59% vs. 0%, P = 0.004). One year after treatment initiation and at final visit, more infliximab-treated patients had an improvement in their ocular inflammation (100% vs. 33%, P = 0.002, and 94% vs. 0%, P<0.001, respectively) and a decreased requirement for topical prednisolone acetate 1% (94% vs. 33%, P = 0.009, and 89% vs. 29%, P = 0.007, respectively) compared with those treated with etanercept. No significant differences in the use of oral corticosteroids and immunosuppressive agents were noted between the 2 groups at 6 months, 1 year, and final visit., Conclusions: Infliximab was more effective than etanercept in the treatment of recalcitrant uveitis and decreased the use of topical steroids.

Purpose: To report the case of a patient with undiagnosed Hodgkin's lymphoma who presented with coexistent unilateral nodular episcleritis and scleritis., Design: Interventional case report and literature review, Methods: Review of clinical history, laboratory findings, histology of episcleral and cervical lymph node biopsies, and follow-up., Results: A 20-year-old female presented with a 5-month history of redness and pain in her left eye, with associated symptoms of dyspnea, malaise, and fever. The patient was found to have multifocal nodular episcleritis and scleritis that was not responsive to topical steroids or systemic nonsteroidal anti-inflammatory treatment. Laboratory tests subsequently revealed evidence of systemic inflammation, and radiologic studies showed extensive mediastinal and cervical adenopathy. A cervical lymph node biopsy showed Reed-Sternberg cells and a chronic lymphocytic infiltrate consistent with nodular sclerosing Hodgkin's lymphoma. Histopathologic analysis of an episcleral nodule revealed a necrotizing granuloma with vasculitis. Systemic chemotherapy was instituted for the Hodgkin's disease; this therapy abolished the nodular scleritis., Conclusions: This case raises the possibility of concurrent undiagnosed systemic vasculitis with only an ocular manifestation with Hodgkin's lymphoma, either as a coincidence or as a paraneoplastic syndrome. Moreover, it emphasizes the important role of tissue biopsy in establishing diagnosis and directing treatment., (Copyright 2003 by the American Academy of Ophthalmology.)

In vitro experiments have shown that endothelial cells can function as antigen-presenting cells to CD4(+) T lymphocytes. The studies presented here address the question of whether naïve versus previously activated CD4(+) helper T cells differ in their responses to endothelial antigen presentation. TCR-transgenic mice were used as a source of naive T cells of defined antigen specificity. These cells were stimulated in vitro with antigen and splenic antigen-presenting cells to generate populations of T lymphocytes with a previously activated/memory phenotype. Two different types of mouse endothelial cells were used as antigen-presenting cells, including the SVEC4-10 line derived from lymph node endothelium and primary murine pulmonary microvascular endothelium. Monolayer cultures of both types of endothelium were capable of antigen-dependent stimulation of previously activated TCR-transgenic CD4(+) cells. In contrast, neither endothelial type could activate naïve CD4(+) T cells. When costimulatory signals were provided in trans by the addition of MHC-mismatched mouse spleen cells, activation of naïve T cells by endothelial antigen presentation could be demonstrated. The expression of ICAM-1 or VCAM-1 on the endothelial cells was not sufficient to activate naïve T cells. Furthermore, the mouse lung endothelium constitutively expresses B7-1, and therefore, the inability of endothelium to stimulate naïve T cells could not be attributed to a lack of CD28-ligands. These studies suggest that the potential role of endothelial antigen presentation in immune responses is restricted to promoting responses by T cells which have previously encountered antigen presented by other antigen-presenting cells., (Copyright 1998 Academic Press.)