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Supplementary Figure 2 from Eradication of Tumor Colonization and Invasion by a B Cell–Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma

Human primary intraocular lymphoma (PIOL) is predominantly a B cell–originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell–specific immunotoxin therapy may have clinical implications in treating human PIOL. (Cancer Res 2006; 66(21): 10586-93)

Supplementary Figure 1 from Eradication of Tumor Colonization and Invasion by a B Cell–Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Purpose To compare the effectiveness of intravitreal injection of triamcinolone acetonide–moxifloxacin (Tri-Moxi) to a standard eyedrop regimen in controlling postoperative inflammation, corneal edema, and the rate of high intraocular pressure (IOP) among cataract patients. Setting Loma Linda University Eye Institute, California, USA. Design Retrospective longitudinal comparative study. Methods The electronic medical records of patients who underwent cataract surgery using triamcinolone acetonide–moxifloxacin injection along with a postoperative nonsteroidal antiinflammatory drug drop were reviewed (Group 1). Group 1 was compared with patients who received a standard eyedrop (Group 2) in terms of intraocular inflammation and corneal edema severity, and the rate of high IOP, postoperatively. Results A total of 1195 consecutive eyes (Group 1 [681 eyes], Group 2 [514 eyes]) of 919 patients were included in the study. The anterior chamber cell reaction severity decreased by 34.0% and 35.7% at 1 week and 1 month, respectively, after surgery following triamcinolone acetonide–moxifloxacin injection compared with standard eyedrop therapy (P = .001 and P = .02, respectively). Group 1 was associated with increased severity of corneal edema (odds ratio, 1.48; P = .001) on postoperative day 1, with no statistically significant difference at 1 week and 1 month postoperatively (P = .25 and P = .48, respectively). There was no statistically significant difference in the rate of high IOP between the two groups at different timepoints postoperatively. Conclusions Triamcinolone acetonide–moxifloxacin injection is an effective method to control intraocular inflammation after cataract surgery. It is a promising substitute for standard eyedrop therapy, especially for patients who have poor compliance with eyedrop usage.

To compare the predictive refractive accuracy of intraoperative aberrometry (ORA) to the preoperative Barrett True-K formula in the calculation of intraocular lens (IOL) power in eyes with prior refractive surgery undergoing cataract surgery at the Loma Linda University Eye Institute, Loma Linda, California, USA. We conducted a retrospective chart review of patients with a history of post-myopic or hyperopic LASIK/PRK who underwent uncomplicated cataract surgery between October 2016 and March 2020. Pre-operative measurements were performed utilizing the Barrett True-K formula. Intraoperative aberrometry (ORA) was used for aphakic refraction and IOL power calculation during surgery. Predictive refractive accuracy of the two methods was compared based on the difference between achieved and intended target spherical equivalent. A total of 97 eyes (69 patients) were included in the study. Of these, 81 eyes (83.5%) had previous myopic LASIK/PRK and 16 eyes (16.5%) had previous hyperopic LASIK/PRK. Median (MedAE)/mean (MAE) absolute prediction errors for preoperative as compared to intraoperative methods were 0.49 D/0.58 D compared to 0.42 D/0.51 D, respectively (P = 0.001/0.002). Over all, ORA led to a statistically significant lower median and mean absolute error compared to the Barrett True-K formula in post-refractive eyes. Percentage of eyes within ± 1.00 D of intended target refraction as predicted by the preoperative versus the intraoperative method was 82.3% and 89.6%, respectively (P = 0.04). Although ORA led to a statistically significant lower median absolute error compared to the Barrett True-K formula, the two methods are clinically comparable in predictive refractive accuracy in patients with prior refractive surgery.

Introduction: Dry eye disease (DED) is an important public health problem considering its prevalence, morbidity, and cost implications. In the last two decades, new insight on the pathogenesis of dry eye has resulted in development of novel therapeutic modalities.Areas covered: This review will discuss current and emerging pharmacological modalities in treatment of DED to include tear supplements, anti-inflammatory therapy, antibiotics, vitamin A, other vitamins and antioxidants, free amino acids, essential fatty acids, hormone replacement therapy, mucolytics, tear stimulation (secretagogues) and biological tear substitutes. In preparing this review, a Medline, PubMed and Cochrane Database search of the medical literature for the period between January 1978 and July 2016 using a wide range of keywords was conducted. Only treatment modalities that had their efficacy and safety investigated in clinical studies are included.Expert commentary: Many patients have multiple mechanisms contributing to DED...

Purpose To compare repeat penetrating keratoplasty (PK) with Boston type I keratoprosthesis (KPro) implantation for full-thickness donor corneal graft failure. Design Previous donor graft failure is a common indication for both PK and KPro implantation. Selection of the surgical procedure is entirely dependent on the surgeon because there are no studies available for guidance. Therefore, a systematic review was undertaken to examine vision, device retention, graft clarity, and postoperative glaucoma and infection outcomes after repeat PK versus KPro implantation. Methods Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States. Visual acuity at 2 years was the primary outcome measure. The proportion of clear grafts in the repeat PK group, device retention in the KPro group, and the development of postoperative glaucoma and infection were secondary outcome measures. Results The search strategy identified 17 128 articles in the PK analysis. After screening, 26 studies (21 case series and 5 cohort studies) were included in the review. Pooled analysis of the 26 unique studies demonstrated a 42% (95% confidence interval [CI], 30%–56%) likelihood of maintaining 20/200 or better at 2 years after repeat PK, compared with an 80% (95% CI, 68%–88%) probability with KPro implantation. The probability of maintaining a clear graft at 5 years was 47% (95% CI, 40%–54%) after repeat PK, whereas the probability of retention of the KPro at 5 years was 75% (95% CI, 64%–84%). The rate of progression of glaucoma at 3 years was 25% (95% CI, 10%–44%) after repeat PK and 30% in the KPro cohort. Conclusions These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK.

The cornea is the most densely innervated mammalian tissue. The sensory nerves are responsible for sensations of dryness, temperature, touch, and pain, and play important roles in the blink reflex, wound healing, and tear production. Many ocular and systemic diseases can adversely affect corneal sensory nerve and consequently impair their function. One of such systemic diseases is diabetes mellitus (DM) which causes sensory degeneration, neurotrophic keratopathy (DNK), and delayed wound healing. In this review, we summarize recent discoveries revealing mechanisms underlying the pathogenesis of DNK and the impairment of sensory nerve regeneration in post wound diabetic corneas in using animal model of human diabetes. Because it is generally believed that common mechanisms are operative in the pathogenesis of diabetic peripheral neuropathy in different tissues, the findings in the corneas have implications in in other tissues such as the skin, which often leads to foot ulceration and amputation in diabetic patients.

Purpose To study resident compliance with the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for primary open-angle glaucoma suspect (POAGS) in a resident ophthalmology clinic. Patients and methods Two hundred charts were selected for analysis of adult patients with the International Classification of Diseases diagnosis code for POAGS during their initial visit between November 2, 2010 and May 6, 2014 at the Kresge Eye Institute resident clinic. Electronic medical records of clinic visits for POAGS patients were evaluated for documentation and compliance with 17 elements of AAO PPPs. Results The overall mean compliance was 73.8% for all charts (n=200), 74.4% for first-year residents (n=53), 74.5% for second-year residents (n=38), and 73.3% for third-year residents (n=109). Documentation rates were high (>90%) for 9 elements, which included most elements of physical examination and history. Documentation of ocular history, central corneal thickness, gonioscopy, optic nerve head and retinal nerve fiber layer analysis, and visual field ranged from 40% to 80%. Documentation was lowest for patient education elements which ranged from 0% to 10%. Compliance was not significantly different (P>0.05) between residents or between different resident years for any element. Conclusions Residents' compliance was high for most elements of the PPPs for POAGS. We identified elements with poor compliance especially regarding patient education. Adherence to AAO PPPs can be a helpful method of assessing resident performance.

Glucocorticoid-induced tumor necrosis factor receptor (GITR), found constitutively expressed on human primary natural killer (NK) cells at low levels was up-regulated upon stimulation by either Toll-like receptor ligand or NK cell growth factor, interleukin (IL)-15. cDNA microarray analysis showed that engagement of GITR primarily suppressed the activation of NF-KB pathway of NK cells and up-regulated anti-inflammatory genes heme oxygenase-1 and IL-10. Further analysis revealed that GITR activation suppressed NK cell proliferation in response to IL-15. GITR activation also suppressed proinflammatory cytokine secretion and increased NK cell apoptosis. GITR activation resulted in blocked phosphorylation of Stat5 and Akt, which may have contributed to the observed antiproliferative effect of GITR on NK cells. Increased apoptosis was independent of the Fas-FasL pathway, but Bcl-XL and phospho-Bad protein expressions were diminished, suggesting involvement of the mitochondrial apoptosis pathway. The results suggest that although GITR is an activation marker for NK cells similar to that for T cells, GITR serves as a negative regulator for NK cell activation. Our studies demonstrate a novel physiological role of GITR on NK cells.

To compare repeat penetrating keratoplasty (PK) with Boston type I keratoprosthesis (KPro) implantation for full-thickness donor corneal graft failure.Previous donor graft failure is a common indication for both PK and KPro implantation. Selection of the surgical procedure is entirely dependent on the surgeon because there are no studies available for guidance. Therefore, a systematic review was undertaken to examine vision, device retention, graft clarity, and postoperative glaucoma and infection outcomes after repeat PK versus KPro implantation.Articles with data regarding repeat PK published between 1990 and 2014 were identified in PubMed, EMBASE, the Latin American and Caribbean Health Sciences Literature Database, and the Cochrane Central Register of Controlled Trials and were reviewed. Results were compared with a retrospective review of consecutive, nonrandomized, longitudinal case series of KPro implantations performed at 5 tertiary care centers in the United States. Visual acuity at 2 years was the primary outcome measure. The proportion of clear grafts in the repeat PK group, device retention in the KPro group, and the development of postoperative glaucoma and infection were secondary outcome measures.The search strategy identified 17 128 articles in the PK analysis. After screening, 26 studies (21 case series and 5 cohort studies) were included in the review. Pooled analysis of the 26 unique studies demonstrated a 42% (95% confidence interval [CI], 30%-56%) likelihood of maintaining 20/200 or better at 2 years after repeat PK, compared with an 80% (95% CI, 68%-88%) probability with KPro implantation. The probability of maintaining a clear graft at 5 years was 47% (95% CI, 40%-54%) after repeat PK, whereas the probability of retention of the KPro at 5 years was 75% (95% CI, 64%-84%). The rate of progression of glaucoma at 3 years was 25% (95% CI, 10%-44%) after repeat PK and 30% in the KPro cohort.These results demonstrate favorable outcomes of KPro surgery for donor corneal graft failure with a greater likelihood of maintaining visual improvement without higher risk of postoperative glaucoma compared with repeat donor PK.

Patients with photosensitive disorders of the skin may present with ocular manifestations that are evident at birth or may be manifested later with progression of the disorder. Dermatologists should be able to recognize these and appropriately refer patients for further management. Ocular involvement associated with immunologically mediated photodermatoses, drug- and chemical-induced photosensitivity, photodermatoses associated with defective DNA repair/chromosome instability, and photoaggravated dermatoses are reviewed. Photodermatoses are commonly classified into four general groups: (1) immunologically mediated photodermatoses; (2) drug- and chemical-induced photosensitivity; (3) photodermatoses associated with defective DNA repair/chromosome instability; and (4) photoaggravated dermatoses. Photodermatoses in these groups with ocular involvement will be discussed. In addition, skin diseases associated with photophobia are also described.

PURPOSE The aim of this study was to determine intertest variability of measurements taken by the Pentacam tomographer in eyes with keratoconus. METHODS Three Pentacam measurements with 1-minute intervals were taken from 101 eyes (81 keratoconus and 20 controls) from 57 patients (47 keratoconus and 10 controls) by the same examiner and under the same conditions. Keratoconus eyes were divided into 3 subgroups based on topographic astigmatism (TA). Variability in astigmatism, mean keratometry, central corneal thickness, and fixation values were compared within the patient subgroups versus normal controls. RESULTS Variability of all studied parameters (astigmatism, mean keratometry, central corneal thickness, and fixation values) increased with increasing TA in patients with keratoconus. CONCLUSIONS Pentacam measurements show increased variability in patients with keratoconus. The degree of variability correlates with TA.

Human primary intraocular lymphoma (PIOL) is predominantly a B cell–originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell–specific immunotoxin therapy may have clinical implications in treating human PIOL. (Cancer Res 2006; 66(21): 10586-93)

PURPOSE: To present a case of unilateral hypopyon uveitis that began 15 days after uneventful bilateral LASIK in a 24-year-old man with an undisclosed history of ulcerative colitis. METHODS: Case report. RESULTS: The hypopyon uveitis completely resolved after treatment with aggressive topical and oral steroid agents in combination with topical antibiotic coverage. CONCLUSIONS: Although rare, visually significant hypopyon uveitis may arise after LASIK in the setting of ulcerative colitis and positive human leukocyte antigen (HLA) B27. Early recognition and treatment can result in an excellent outcome. The exact relationship between hypopyon uveitis and LASIK is impossible to ascertain.

Purpose To evaluate the refractive error quality of life (RQL) improvement, patient satisfaction, and clinical results of laser refractive surgery performed by residents or fellows. Setting Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA. Design Case series. Methods This study reviewed the clinical results of consecutive refractive surgery cases performed between March 2010 and February 2012 by ophthalmology residents or fellows. One-year postoperative analysis of the RQL and patient satisfaction in a subgroup of patients was completed using the National Eye Institute Refractive Error Correction Quality of Life-42 instrument (NEI RQL-42), and a comparison with NEI published normative data and post-refractive data was performed. Results Data were obtained from 138 eyes that had laser in situ keratomileusis and 4 eyes that had photorefractive keratectomy. The 1-year postoperative analysis of the RQL and patient satisfaction was completed in 34 patients. After 6 months postoperatively, the mean uncorrected distance visual acuity was 0.01 logMAR (95% confidence interval [CI], −0.012 to 0.023). The mean postoperative residual refractive error spherical equivalent was −0.20 diopter (D) (95% CI, −0.26 to −0.13). No eye lost corrected distance visual acuity. Equivalent or better satisfaction in the RQL was found in all but 1 of the 13 scale scores of the NEI RQL-42 compared with previously published NEI data. Conclusions Laser refractive surgery performed by residents and fellows showed high patient satisfaction and an improved RQL 1-year postoperatively. Clinical outcomes validated the safety and efficacy of refractive surgery performed by surgeons in training. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

A 76-year-old man presented atypically with a 4-week history of a rapidly enlarging ulcerated nodular lesion of the left upper eyelid that was found to be sebaceous cell carcinoma. Further investigation showed no metastatic disease, and Mohs surgery was performed to resect the tumor. Histopathologic analysis showed features diagnostic of sebaceous cell carcinoma. However, most of the mass consisted of xanthomatous granulomatous inflammatory reaction vastly out of proportion with the tumor burden. The patient was spared from orbital exenteration, and no evidence of recurrence was present 6 months after resection.

To evaluate CD4(+)Foxp3(+) (forkhead box P3) T-regulatory cell populations in patients with uveitis and to determine if T-regulatory cell populations are associated with disease features.Patients with uveitis were evaluated for CD4(+)Foxp3(+) T-regulatory cells by flow cytometry. Systemic and ocular diagnoses, disease activity, and the presence of cystoid macular edema were reviewed. Percentages of CD4(+)Foxp3(+) lymphocytes were compared for patients with inactive vs active disease, systemic vs ocular diagnoses, and the presence or absence of cystoid macular edema. Real-time polymerase chain reaction testing was performed on 2 patients with extremely low CD4(+)Foxp3(+) cell populations to assess Foxp3 mRNA.A total of 20 patients with intermediate uveitis, posterior uveitis, and panuveitis were evaluated. The mean age was 40.6 years and the mean visual acuity was 20/57. Percentages of CD4(+)Foxp3(+) cells were lower in patients with active compared with inactive uveitis (P.05). No differences in T-regulatory cells were observed between the other subgroups. Two patients with recalcitrant uveitis who demonstrated less than 1% CD4(+)Foxp3(+) lymphocytes showed extremely low or absent Foxp3 mRNA.T-regulatory cells are reduced in patients with active compared with inactive disease. Severe depletion of CD4(+)Foxp3(+) T cells and Foxp3 mRNA in 2 patients with severe uveitis suggests that loss of the T-regulatory cells of uveitis may be a salient feature in certain patients.