Daniel Albert

J Ocul Pharmacol Ther. 2021 Dec;37(10):545-555. doi: 10.1089/jop.2021.0015. Epub 2021 Sep 28.

ABSTRACT

Purpose: Instability of the tear film leads to evaporative dry eye disease (EDED), but the Harderian gland in some terrestrial vertebrates may produce novel lipids that stabilize the tear film and protect against dry eye. Here, the nonpolar lipids in the Harderian gland and tears of the rabbit but absent in human tears were identified and tested in preclinical studies to determine whether they could treat severe EDED. Methods: Lipids were identified primarily by atmospheric pressure chemical ionization mass spectrometry (MS) and fragmentation MS/MS. An identified lipid was synthesized and formulated as an emulsion and as a cyclodextrin (CD) clathrate. Following doses with test agents and controls, tear film breakup time (TBUT), tear production, corneal fluorescein staining, macrophage infiltration, and goblet cell survival were measured using standard tests at 0, 2 and 4 weeks in an animal model of EDED. Results: The lipid emulsion increased TBUT (P < 0.01) and tear production (P < 0.05), while it decreased corneal staining (P < 0.01) compared to controls. The lipid CD formulation increased TBUT (P < 0.05) and tear production (P < 0.05) but had no significant effect on the remaining test parameters. There were no differences in macrophage infiltration and conjunctival impression cytology scores between the formulations and their vehicle controls. Conclusions: Lipids in the rabbit Harderian gland and tears differ from those identified in human meibum and tears. These unique rabbit lipids may confer a protective effect against EDED and, as supplements to human tears, fulfill a similar role.

PMID:34590914 | PMC:PMC8713569 | DOI:10.1089/jop.2021.0015

Am J Surg Pathol. 2020 Aug;44(8):1005-1016. doi: 10.1097/PAS.0000000000001462.

ABSTRACT

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

PMID:32452870 | PMC:PMC7953758 | DOI:10.1097/PAS.0000000000001462

Exp Eye Res. 2020 Jun;195:108030. doi: 10.1016/j.exer.2020.108030. Epub 2020 Apr 6.

ABSTRACT

Retinopathy of prematurity (ROP) is a growing cause of lifelong blindness and visual defects as improved neonatal care worldwide increases survival in very-low-birthweight preterm newborns. Advancing ROP is managed by laser surgery or a single intravitreal injection of anti-VEGF, typically at 33-36 weeks gestational age. While newer methods of scanning and telemedicine improve monitoring ROP, the above interventions are more difficult to deliver in developing countries. There is also concern as to laser-induced detachment and adverse developmental effects in newborns of anti-VEGF treatment, spurring a search for alternative means of mitigating ROP. Pigment epithelium-derived factor (PEDF), a potent angiogenesis inhibitor appears late in gestation, is undetected in 25-28 week vitreous, but present at full term. Its absence may contribute to ROP upon transition from high-to-ambient oxygen environment or with intermittent hypoxia. We recently described antiangiogenic PEDF-derived small peptides which inhibit choroidal neovascularization, and suggested that their target may be laminin receptor, 67LR. The latter has been implicated in oxygen-induced ischemic retinopathy (OIR). Here we examined the effect of a nonapeptide, PEDF 336, in a newborn mouse OIR model. Neovascularization was significantly decreased in a dose-responsive manner by single intravitreal (IVT) injections of 1.25-7.5 μg/eye (1.0-6.0 nmol/eye). By contrast, anti-mouse VEGFA₁₆₄ was only effective at 25 ng/eye, with limited dose-response. Combination of anti-VEGFA₁₆₄ with PEDF 336 gave only the poorer anti-VEGF response while abrogating the robust inhibition seen with peptide-alone, suggesting a need for VEGF in sensitizing the endothelium to the peptide. VEGF stimulated 67LR presentation on endothelial cells, which was decreased in the presence of PEDF 336. Mouse and rabbit eyes showed no histopathology or inflammation after IVT peptide injection. Thus, PEDF 336 is a potential ROP therapeutic, but is not expected to be beneficial in combination with anti-VEGF.

PMID:32272114 | PMC:PMC7282953 | DOI:10.1016/j.exer.2020.108030

Ophthalmology. 2020 Apr;127(4S):S148-S157. doi: 10.1016/j.ophtha.2020.01.032.

ABSTRACT

OBJECTIVE: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I¹²⁵) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial.

DESIGN: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial.

PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension.

METHODS: I¹²⁵ brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis.

MAIN OUTCOME MEASURES: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation.

RESULTS: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08).

CONCLUSIONS: Local treatment failure and enucleation were relatively infrequent events after I¹²⁵ brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

PMID:32200815 | DOI:10.1016/j.ophtha.2020.01.032

Case Rep Ophthalmol. 2019 May 23;10(2):180-185. doi: 10.1159/000500662. eCollection 2019 May-Aug.

ABSTRACT

Muir-Torre syndrome, a variant of Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an autosomal dominant disease characterized by skin neoplasms (sebaceous or keratoacanthomas) and visceral malignancies. Due to the rarity of the syndrome there are no firm guidelines on how and when to test patients with its typical skin lesions. We describe a case that highlights the importance of a detailed family history.

PMID:31692600 | PMC:PMC6760355 | DOI:10.1159/000500662

Exp Eye Res. 2019 Nov;188:107798. doi: 10.1016/j.exer.2019.107798. Epub 2019 Sep 11.

ABSTRACT

Abnormal migration and proliferation of endothelial cells (EC) drive neovascular retinopathies. While anti-VEGF treatment slows progression, pathology is often supported by decrease in intraocular pigment epithelium-derived factor (PEDF), an endogenous inhibitor of angiogenesis. A surface helical 34-mer peptide of PEDF, comprising this activity, is efficacious in animal models of neovascular retina disease but remains impractically large for therapeutic use. We sought smaller fragments within this sequence that mitigate choroidal neovascularization (CNV). Expecting rapid intravitreal (IVT) clearance, we also developed a method to reversibly attach peptides to nano-carriers for extended delivery. Synthetic fragments of 34-mer yielded smaller anti-angiogenic peptides, and N-terminal capping with dicarboxylic acids did not diminish activity. Charge restoration via substitution of an internal aspartate by asparagine improved potency, achieving low nM apoptotic response in VEGF-activated EC. Two optimized peptides (PEDF 335, 8-mer and PEDF 336, 9-mer) were tested in a mouse model of laser-induced CNV. IVT injection of either peptide, 2-5 days before laser treatment, gave significant CNV decrease at day +14 post laser treatment. The 8-mer also decreased CNV, when administered as eye drops. Also examined was a nanoparticle-conjugate (NPC) prodrug of the 9-mer, having positive zeta potential, expected to display longer intraocular residence. This NPC showed extended efficacy, even when injected 14 days before laser treatment. Neither inflammatory cells nor other histopathologic abnormalities were seen in rabbit eyes harvested 14 days following IVT injection of PEDF 336 (>200 μg). No rabbit or mouse eye irritation was observed over 12-17 days of PEDF 335 eye drops (10 mM). Viability was unaffected in 3 retinal and 2 choroidal cell types by PEDF 335 up to 100 μM, PEDF 336 (100 μM) gave slight growth inhibition only in choroidal EC. A small anti-angiogenic PEDF epitope (G-Y-D-L-Y-R-V) was identified, variants (adipic-Sar-Y-N-L-Y-R-V) mitigate CNV, with clinical potential in treating neovascular retinopathy. Their shared active motif, Y - - - R, is found in laminin (Ln) peptide YIGSR, which binds Ln receptor 67LR, a known high-affinity ligand of PEDF 34-mer.

PMID:31520600 | PMC:PMC7032632 | DOI:10.1016/j.exer.2019.107798

Ophthalmic Plast Reconstr Surg. 2019 Sep/Oct;35(5):e115-e116. doi: 10.1097/IOP.0000000000001443.

ABSTRACT

A 7-year-old healthy girl presented for an evaluation of a left vascular scleral mass. The lesion appeared spontaneously with no history of trauma, coagulopathy, or topical medication use. It was nontender, enlarging, and did not extend intraocularly. Her OS vision was 20/20, and the remainder of her eye examination was normal. Evaluation of the ocular mass included B-scan ultrasound, ultrasound biomicroscopy, anterior segment optical coherence tomography (OCT), and orbital MRI. The anterior segment OCT demonstrated vessels within the mass with no defined capsule. The orbital MRI confirmed a lesion isolated to the scleral layers of the globe, with low blood flow. The patient had a partial response to oral propranolol. Because the lesion vessels began to extend into her corneal endothelium, there was a concern for malignancy. A biopsy confirmed a benign intrascleral capillary hemangioma. Discontinuation of the propranolol demonstrated stability of the lesion 6 months later.

PMID:31503170 | DOI:10.1097/IOP.0000000000001443

Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4071-4081. doi: 10.1167/iovs.18-24087.

ABSTRACT

PURPOSE: Drug delivery by intravitreal injection remains problematic, small agents and macromolecules both clearing rapidly. Typical carriers use microparticles (>2 μm), with size-related liabilities, to slow diffusion. We recently described cationic nanoparticles (NP) where conjugated Arg peptides prolonged residence in rat eyes, through ionic interaction with vitreal poly-anions. Here we extended this strategy to in vivo tracking of NP-conjugate (NPC) clearance from rabbit eyes. Relating t1/2 to zeta potential, and varied dose, we estimated the limits of this charge-based delivery system.

METHODS: NPC carried covalently attached PEG8-2Arg or PEG8-3Arg pentapeptides, having known sequences from human eye proteins. Peptides were conjugated (61-64 per NPC); each NP/NPC also carried a cyanine7 tag (<0.5 dye/particle). In vivo imaging system (IVIS), after intravitreal injection, estimated NPC loss by 800-nm photon emission (745-nm excitation) at 1 to 3-week intervals following initial scan at day 10.

RESULTS: NPC of 2Arg-peptides or 3Arg-peptides showed clearance t1/2 of 7 days and 17 days respectively, unconjugated NP t1/2 was <<5 days. Doses of 90, 180, and 360 μg of PEG8-2Arg NPC were compared. The lower doses showed dose-proportional day-10 concentration, and similar clearance. Higher early loss was seen with a 360-μg dose, exceeding rabbit vitreal binding capacity. No inflammation was observed.

CONCLUSIONS: This type of cationic NPC can safely increase residence t1/2 in a 1 to 3-week range, with dose <100 μg per mL vitreous. Human drug load may then range from 10 to 100 μg/eye, usefulness depending on individual drug potency and release rate, superimposed on extended intravitreal residence.

PMID:30098194 | PMC:PMC6088811 | DOI:10.1167/iovs.18-24087

Ocul Oncol Pathol. 2017 Dec;4(1):52-56. doi: 10.1159/000475994. Epub 2017 Jul 19.

ABSTRACT

BACKGROUND/AIMS: Establish a reliable rabbit dry eye (DE) model.

METHODS: An interventional cohort study surgically removing glands contributing to the tear film. Eight rabbits were studied after removal of left lacrimal, Harderian, or both glands. Additional rabbits had Meibomian glands in the left eye thermally obstructed. All were followed for 10 weeks with phenol red thread (PRT) and slit-lamp examination with 2% fluorescein. We assessed corneal sensitivity using a Cochet-Bonnet esthesiometer. Outcome measures were severity/duration of reduced PRT, punctate epithelial erosions (PEE), and histologic evidence of corneal pannus.

RESULTS: Fluorescein staining demonstrated signs of dryness including PEE in all of the interventional eyes. The subjective measurement of epithelial erosions correlated with decreased tear production. PRT measurements in the control eyes averaged 31.54 mm (±1.83) and 22.71 mm (±1.60) in the eight left eyes, without loss of corneal sensitivity.

CONCLUSIONS: Surgical removal of either the Harderian or lacrimal gland results in statistically significant decreases in tear volume and the development of severe DE. Removal of both glands results in the occurrence of a DE of comparable severity/duration to removal of either the lacrimal or Harderian gland alone. Meibomian gland obstruction contributes less to the DE model.

PMID:29344500 | PMC:PMC5757560 | DOI:10.1159/000475994

Ocul Oncol Pathol. 2017 Nov;3(4):259-261. doi: 10.1159/000461586. Epub 2017 Mar 24.

ABSTRACT

During the planning meeting for the Collaborative Ocular Melanoma Study (COMS) prior to the start of patient recruitment in 1986, there was an interest expressed in determining whether a relationship existed between the presence of uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the ophthalmic examination form (unlike the pathology form for enucleated eyes) for each COMS patient asked whether AH was present or not. Though an increased prevalence was not found, this result was never published. A recent unpublished study at the University of Wisconsin School of Veterinary Medicine indicated a higher prevalence of AH in canine eyes with UM when compared to control eyes (without tumor) enucleated for goniodysgenesis. This further increased our interest in revisiting the published literature, clinical records, and histopathology slides of the enucleated eyes from the COMS study, as well as the histopathology slides on file in the University of Wisconsin Eye Pathology Laboratory. While cases with both AH and UM were occasionally encountered in the literature, clinically, we could not find a previous study focusing on these two processes. This study was conducted to explore whether such an association exists.

PMID:29344477 | PMC:PMC5757614 | DOI:10.1159/000461586

Orbit. 2018 Jun;37(3):208-211. doi: 10.1080/01676830.2017.1383476. Epub 2017 Oct 20.

ABSTRACT

Neurofibromatosis type 1 (NF1) is an inherited disorder often associated with optic nerve gliomas, low-grade brain tumors, and readily visible signs. Though these features are frequently emphasized, the psychosocial and emotional morbidities are often overlooked. We present a patient with depressive disorder resulting in suicide in a patient with NF1.

PMID:29053048 | DOI:10.1080/01676830.2017.1383476

Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5142-5150. doi: 10.1167/iovs.17-22160.

ABSTRACT

PURPOSE: Intravitreal injection of antiangiogenic agents is becoming a standard treatment for neovascular retinal diseases. Sustained release of therapeutics by injecting colloidal carriers is a promising approach to reduce the injection frequency, which reduces treatment burdens and the risk of complications on patients. Such sustained release often requires carriers to have micrometer-scale dimension that, however, can potentially promote glaucoma and inflammation. Small, polycationic particles can be immobilized in vitreous through multiple cooperative ionic interactions with hyaluronic acid of the vitreous interior, but such particles are generally toxic. Here, we synthesized and examined a biocompatible dextran-based nanocarrier (<50 nm in diameter) conjugated with cationic peptides containing L-arginine with minimal toxicity, aiming to provide sustained release of therapeutic drugs in vitreous.

METHODS: We synthesized the nanocarriers with condensed cholesteryl dextran (CDEX) as core material. Cationic peptides containing 1 to 4 arginine groups, along with fluorescence tags, were conjugated to the CDEX surface. We monitored the carrier diffusion rate ex vivo and half-lives in vivo in rodent vitreous using fluorescence imaging. We evaluated the toxicity by histological examinations at the second, third, eighth, and thirty-sixth week.

RESULTS: The diffusion rate of nanocarriers was inversely related to zeta potential values in freshly isolated vitreous humor. We observed increased half-lives in vivo with increasing zeta potential (up to 240 days). Histological examinations confirmed no adverse effects on ocular morphology and organization.

CONCLUSIONS: We demonstrated the potential of L-arginine peptide-conjugated nanocarriers toward safe and sustained therapeutic release system for posterior eye diseases.

PMID:28986592 | PMC:PMC5634351 | DOI:10.1167/iovs.17-22160

Ocul Oncol Pathol. 2017 Jan;3(1):60-65. doi: 10.1159/000449466. Epub 2016 Oct 15.

ABSTRACT

AIMS: The aim of this paper was to identify the location and to grade the severity of most significant inflammation within positive temporal artery biopsies along with other key clinical and histologic characteristics.

METHODS: Charts and pathology slides for 70 patients diagnosed with temporal arteritis at the University of Wisconsin (UW) Hospital and Clinics from 1989 to 2015 were reviewed. A subset of 48 specimens was immunostained for CD68 and graded on a scale from 0 to +++; the location of staining was recorded.

RESULTS: The most severe granulomatous inflammation was in the media and adventitia in 13% (9/70) of the biopsies; the remaining had uniform full thickness inflammation. Of the slides that were stained with CD68, 94% (45/48) were positive. In 42% (19/45), the stained cells were found mainly in the muscularis and adventitia. Seven percent (3/45) of the slides had staining solely around the internal elastic lamina, and 2% (1/45) had staining limited to the intima.

CONCLUSIONS: With a few exceptions, granulomatous inflammation in positive temporal artery biopsies is most evident at the media and adventitia or is uniform throughout the layers of the artery. Our study lends support to the theory that the muscularis and adventitia may play an inciting role in the pathogenesis of temporal arteritis.

PMID:28275606 | PMC:PMC5318845 | DOI:10.1159/000449466

Ophthalmology. 2017 May;124(5):744-745. doi: 10.1016/j.ophtha.2016.11.038. Epub 2017 Jan 19.

NO ABSTRACT

PMID:28110951 | PMC:PMC5517079 | DOI:10.1016/j.ophtha.2016.11.038

Microbiol Spectr. 2016 Nov;4(6):10.1128/microbiolspec.TNMI7-0001-2016. doi: 10.1128/microbiolspec.TNMI7-0001-2016.

ABSTRACT

Ocular tuberculosis is an extrapulmonary mycobacterial infection with variable manifestations. The reported incidence of ocular involvement varies considerably, depending on the criteria used for diagnosis and the population sampled. However, tuberculosis is thought to affect the lungs in 80% of patients, with the remaining 20% being affected in other organs, such as the eye. It is imperative for physicians to consider this diagnosis in their differential, as ocular tuberculosis can present in a fashion similar to that of more common conditions causing ocular inflammation. In addition, prompt recognition of the clinical signs and symptoms leads to quicker initiation of antituberculosis therapy.

PMID:27837746 | PMC:PMC5180603 | DOI:10.1128/microbiolspec.TNMI7-0001-2016

Ophthalmic Plast Reconstr Surg. 2016 Nov/Dec;32(6):e150-e151. doi: 10.1097/IOP.0000000000000343.

ABSTRACT

A 6-year-old girl presented with a left nodular mass around the punctum. Previous debulking in a similar location at 10 weeks and 8 months of age confirmed fibrous hamartoma of infancy. Pathology at the initial surgery revealed benign-appearing fibroadipose tissue, vasculature, and smooth muscle. Pathologic examination from the third debulking illustrated less fibrous trabeculae extending into increased amounts of mature-appearing adipocytes with collections of immature-appearing fibrocytes. The lesion had slight differences in pathology compared with prior surgical specimens; however, was still consistent with fibrous hamartoma of infancy. No recurrence has been reported since the last surgery.

PMID:27654620 | DOI:10.1097/IOP.0000000000000343

Ocul Oncol Pathol. 2016 Apr;2(3):171-7. doi: 10.1159/000442352. Epub 2016 Jan 27.

ABSTRACT

PURPOSE: The aim of this study was to use massively parallel DNA sequencing to identify GNAQ/11, BAP1 and SF3B1 mutations in ophthalmic melanocytoma.

PROCEDURES: Six ophthalmic melanocytoma specimens (1 iridociliary and 5 optic nerve) were profiled for genomic alterations in GNAQ/11, BAP1 and SF3B1 using a custom deep sequencing assay. This assay uses solution phase hybridization-based exon capture and deep-coverage massively parallel DNA sequencing to interrogate all protein-coding exons and select introns.

RESULTS: The only iridociliary melanocytoma showed a mutation in GNAQ but not in BAP1. Of the 2 optic-nerve melanocytomas that developed into melanoma, one had a GNAQ mutation and both a BAP1 mutation and monosomy 3. The remaining 3 optic-nerve melanocytomas did not reveal mutations in GNAQ/11 or BAP1. SF3B1 mutations were not detected in any specimen.

CONCLUSIONS: The presence of GNAQ mutation in some iridociliary and optic-nerve melanocytomas suggests a possible relationship between ophthalmic melanocytoma and other ophthalmic melanocytic neoplasms. BAP1 mutation may accompany the transformation of ophthalmic melanocytoma to melanoma.

PMID:27239460 | PMC:PMC4881266 | DOI:10.1159/000442352

Am J Ophthalmol Case Rep. 2016 Apr;1:34-37. doi: 10.1016/j.ajoc.2016.03.006.

ABSTRACT

PURPOSE: The aim of this study was to report a case of Adult-Onset Asthma with Periocular Xanthogranulomas (AAPOX) associated with systemic IgG4-related disease (IgG4-RD).

OBSERVATIONS: A 57-year-old man presented with bilateral periorbital swelling for 1 year. Histopathology of a left orbital biopsy showed fibro vascular connective tissue inundated with foamy, lipid-laden histiocytes and touton giant cells with lymphocytic inflammation. Additional stains revealed CD68 positivity, and S100 negativity. The IgG and IgG4 stained slides showed increased IgG4 positive plasma cells but did not meet the criteria for IgG4-related orbital disease. His IgG4 serology was elevated, and IgG4 staining of his tissue previously diagnosed as autoimmune sclerosing pancreatitis was found to meet the criteria for IgG4-RD.

CONCLUSIONS AND IMPORTANCE: AAPOX can be associated with systemic IgG4-RD.

PMID:27152364 | PMC:PMC4852489 | DOI:10.1016/j.ajoc.2016.03.006

Ophthalmic Plast Reconstr Surg. 2017 May/Jun;33(3S Suppl 1):S72-S73. doi: 10.1097/IOP.0000000000000665.

ABSTRACT

The aim of this study is to report a case of bilateral primary mucinous carcinoma of the eyelids. This is a case report and literature review. A 71-year-old female presented with primary mucinous carcinoma of the left upper eyelid, which was excised with Mohs surgery. One year later, she developed primary mucinous carcinoma of the right upper eyelid, which was also treated Mohs surgery. Extensive workup was negative for evidence of an unknown primary carcinoma or metastasis. Primary mucinous carcinoma of the eyelids may occur as multifocal tumors, and bilateral disease is not necessarily indicative of metastatic disease.

PMID:26950474 | PMC:PMC5011029 | DOI:10.1097/IOP.0000000000000665

Ophthalmology. 2015 Oct;122(10):1955-7. doi: 10.1016/j.ophtha.2015.05.037.

NO ABSTRACT

PMID:26398047 | DOI:10.1016/j.ophtha.2015.05.037

Ophthalmology. 2015 Sep;122(9):1916. doi: 10.1016/j.ophtha.2015.06.048.

NO ABSTRACT

PMID:26299724 | DOI:10.1016/j.ophtha.2015.06.048

Ophthalmology. 2015 Sep;122(9):1765-70. doi: 10.1016/j.ophtha.2015.05.028. Epub 2015 Jun 27.

ABSTRACT

PURPOSE: The purpose of this study was to determine in which species and under what conditions lens tumors occur.

DESIGN: A review of databases of available human and veterinary ocular pathologic material and the previously reported literature.

PARTICIPANTS: Approximately 18 000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health between 1920 and 2014 and 45 000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin between 1983 and 2014.

METHODS: Material in 2 major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as a new growth of tissue characterized by progressive, uncontrolled proliferation of cells. In addition, cases presented at 3 major eye pathologic societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the institutional review board to carry out this study was obtained.

MAIN OUTCOME MEASURES: The presence of tumors of the lens.

RESULTS: The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. In the veterinary school database, 4.5% of feline intraocular and adnexal neoplasms (234/5153) were designated as feline ocular posttraumatic sarcoma, a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All 4 species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation.

CONCLUSIONS: Our results suggest that lens tumors do not occur in humans. In contrast, after lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists that prevents lens tumors in humans.

PMID:26130328 | PMC:PMC4549210 | DOI:10.1016/j.ophtha.2015.05.028

Ophthalmology. 2015 Jun;122(6):1067-9. doi: 10.1016/j.ophtha.2014.11.020.

NO ABSTRACT

PMID:26008907 | DOI:10.1016/j.ophtha.2014.11.020

Ophthalmology. 2014 Dec;121(12):e71. doi: 10.1016/j.ophtha.2014.06.025. Epub 2014 Nov 24.

NO ABSTRACT

PMID:25459470 | DOI:10.1016/j.ophtha.2014.06.025

Molecules. 2014 Oct 30;19(11):17578-603. doi: 10.3390/molecules191117578.

ABSTRACT

The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch's membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.

PMID:25361423 | PMC:PMC4313391 | DOI:10.3390/molecules191117578

Ophthalmology. 2014 Aug;121(8):1493-4. doi: 10.1016/j.ophtha.2014.06.010.

NO ABSTRACT

PMID:25088992 | DOI:10.1016/j.ophtha.2014.06.010

Ophthalmology. 2014 Jun;121(6):1157-9. doi: 10.1016/j.ophtha.2014.04.003.

NO ABSTRACT

PMID:24893767 | DOI:10.1016/j.ophtha.2014.04.003

Ophthalmology. 2014 Sep;121(9):e48. doi: 10.1016/j.ophtha.2014.03.034. Epub 2014 May 1.

NO ABSTRACT

PMID:24793522 | DOI:10.1016/j.ophtha.2014.03.034

Ophthalmology. 2014 Apr;121(4):807-8. doi: 10.1016/j.ophtha.2013.12.031.

NO ABSTRACT

PMID:24694521 | DOI:10.1016/j.ophtha.2013.12.031

JAMA Ophthalmol. 2014 May;132(5):633-6. doi: 10.1001/jamaophthalmol.2013.8243.

ABSTRACT

IMPORTANCE: To report the clinical and histopathologic findings of ocular adnexal angiolymphoid hyperplasia with eosinophilia, an unusual but often misdiagnosed benign disorder.

OBSERVATIONS: The ophthalmologic findings of angiolymphoid hyperplasia with eosinophilia with ocular adnexal involvement are variable and include eyelid swelling, ptosis, proptosis, and loss of vision. Imaging studies typically reveal a well-circumscribed mass in the orbit. The condition may resemble other diseases that involve the orbit and ocular adnexal tissue, such as lymphoma, hemangioma, sarcoidosis, and dermoid cyst. Histopathologic analysis reveals marked vascular proliferation with an accompanying inflammation composed of numerous eosinophils, lymphocytes, and plasma cells.

CONCLUSIONS AND RELEVANCE: Angiolymphoid hyperplasia with eosinophilia is a rare disease that can affect the ocular adnexal tissue. The clinical presentation is often nonspecific; therefore, histopathologic studies are essential for diagnosis and subsequent management of this benign condition.

PMID:24676051 | PMC:PMC4431616 | DOI:10.1001/jamaophthalmol.2013.8243

J Environ Pathol Toxicol Oncol. 2013;32(3):241-4. doi: 10.1615/jenvironpatholtoxicoloncol.2013007532.

ABSTRACT

The effectiveness of saline injection in reducing the toxicity profile of calcitriol when coadministered in mice was evaluated. Mortality was used as an end point to study the toxic effects of calcitriol; the relative risk of mortality in mice injected with saline was evaluated from our previously published animal experiments. We discovered that coadministration with 0.25 mL normal saline solution injected intraperitoneally is associated with a lower mortality rate than calcitriol given alone. The estimated relative risk of mortality was 0.0789 (95% confidence interval, 0.0051-1.22; z = 1.82; P = 0.070) when saline is administered with calcitriol compared to calcitriol alone. There was a reduction in serum calcium levels in mice that received saline (11.4 ± 0.15 mg/dL) compared to mice that did not receive saline (12.42 ± 1.61 mg/dL). Hydration with saline seems to reduce mortality and toxicity in mice receiving calcitriol. Given the decrease in mortality rates, intraperitoneal injections of saline should be considered in studies involving mice receiving injections of calcitriol.

PMID:24266410 | PMC:PMC4016973 | DOI:10.1615/jenvironpatholtoxicoloncol.2013007532

JAMA Ophthalmol. 2013 Nov;131(11):1468-70. doi: 10.1001/jamaophthalmol.2013.5073.

ABSTRACT

IMPORTANCE: To establish that the intracranial and ophthalmologic findings present in victims of abusive head trauma can also be seen in shaken adults.

OBSERVATIONS: We report 2 cases of shaken adults with intracranial and ophthalmologic findings that resulted from repetitive acceleration-deceleration injury. These findings included intracranial hemorrhages, hemorrhages involving the optic nerve sheath, intraretinal and subretinal hemorrhages, and macular folds.

CONCLUSIONS AND RELEVANCE: The intracranial and ophthalmologic findings that are characteristic of abusive head trauma--subdural hemorrhages, optic nerve sheath hemorrhages, and retinal hemorrhages--are generally thought to be limited to young children and infants. Adults may also be victims of shaking abuse, and an ophthalmic examination may be beneficial when shaking is suspected.

PMID:24077385 | PMC:PMC4049539 | DOI:10.1001/jamaophthalmol.2013.5073

Orbit. 2013 Dec;32(6):389-91. doi: 10.3109/01676830.2013.822899. Epub 2013 Aug 19.

ABSTRACT

The purpose of this report is to describe the clinical, radiographica, and histopathologic findings in two pediatric patients with orbital IgG4-related disease.

PMID:23957841 | DOI:10.3109/01676830.2013.822899

Surv Ophthalmol. 2013 Mar-Apr;58(2):196-9. doi: 10.1016/j.survophthal.2012.08.005. Epub 2012 Dec 6.

NO ABSTRACT

PMID:23218807 | DOI:10.1016/j.survophthal.2012.08.005

Arch Ophthalmol. 2012 Oct;130(10):1337-9. doi: 10.1001/archophthalmol.2012.2305.

NO ABSTRACT

PMID:23044955 | DOI:10.1001/archophthalmol.2012.2305

JAMA. 2012 Jul 4;308(1):39-40. doi: 10.1001/jama.2012.6763.

ABSTRACT

For the past 50 years, the “shaken baby” syndrome (SBS) has been one of the many terms used to describe a form of abusive head trauma in children. The term now preferred is pediatric abusive head trauma (AHT), which is defined as “an injury to the skull or intracranial contents of an infant or young child (less than five years of age) due to inflicted blunt impact and/or violent shaking.”^, This new term reflects the fundamental construct that certain forms of head trauma are intentionally inflicted. The incidence is estimated to be 20 to 30 cases per 100,000 children under one year of age with a case fatality rate exceeding 20% and significant disability for about two-thirds of the survivors. In addition, AHT results in major healthcare costs for the survivors. (see Libby AM, Sills MR, Thurston NK, Orton HD. Costs of childhood physical abuse: comparing inflicted and unintentional traumatic brain injuries.

PMID:22760288 | PMC:PMC3660987 | DOI:10.1001/jama.2012.6763

Arch Ophthalmol. 2012 Mar;130(3):336-41. doi: 10.1001/archopthalmol.2011.1503.

ABSTRACT

OBJECTIVES: To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is downregulated during progression of uveal melanoma and whether administration of TSP1 and/or its antiangiogenic peptides attenuate tumor growth.

METHODS: Tyrosinase-SV40 T-antigens (Tyr Tag) transgenic mice were used for evaluation of TSP1 expression during tumor progression using immunohistological methods. The therapeutic potential of TSP1 on tumor progression was evaluated either by crossing Tyr Tag mice with a line of transgenic mice overexpressing TSP1 in the eye or by administration of TSP1-mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software (Media Cybernetics, Inc).

RESULTS: The Tyr Tag tumors from 3-week-old mice showed significant TSP1 expression, which was dramatically downregulated in tumors from 12-week-old mice. Furthermore, the development and progression of tumor was significantly delayed in Tyr Tag TSP1 transgenic mice or Tyr Tag mice receiving TSP1-mimetic peptide (100 mg/kg/d).

CONCLUSIONS: Expression of TSP1 was decreased with the angiogenic switch during progression of uveal melanoma, and TSP1 and/or its antiangiogenic peptides were effective in attenuation of tumor growth.

CLINICAL RELEVANCE: Modulation of TSP1 expression and/or activity may be beneficial in treating uveal melanoma.

PMID:22411663 | PMC:PMC3381901 | DOI:10.1001/archopthalmol.2011.1503

J Agric Food Chem. 2011 May 11;59(9):4979-86. doi: 10.1021/jf104901g. Epub 2011 Apr 12.

ABSTRACT

Resveratrol, a nontoxic polyphenol, has been shown to inhibit tumor growth in a xenograft mouse model of neuroblasoma. However, resveratrol is rapidly metabolized, mainly to its glucuronidated and sulfated derivatives. This study demonstrates that resveratrol alone, and not the glucuronidated or sulfated metabolites, is taken up into tumor cells, induces a rise in [Ca(2+)](i), and ultimately leads to a decrease in tumor cell viability. A new water-soluble resveratrol formulation was delivered directly at the site of the tumor in a neuroblastoma mouse model. The amount of unmodified resveratrol associated with the tumor increased more than 1000-fold. The increase of unmodified resveratrol associated with the tumor resulted in tumor regression. The number of residual tumor cells that remained viable also decreased as the ratio of the metabolites relative to unmodified resveratrol declined.

PMID:21401048 | PMC:PMC3099401 | DOI:10.1021/jf104901g

Eye (Lond). 2011 Jan;25(1):1-14. doi: 10.1038/eye.2010.149. Epub 2010 Oct 29.

ABSTRACT

The ability of light to enact damage on the neurosensory retina and underlying structures has been well understood for hundreds of years. While the eye has adapted several mechanisms to protect itself from such damage, certain exposures to light can still result in temporal or permanent damage. Both clinical observations and laboratory studies have enabled us to understand the various ways by which the eye can protect itself from such damage. Light or electromagnetic radiation can result in damage through photothermal, photomechanical, and photochemical mechanisms. The following review seeks to describe these various processes of injury and many of the variables, which can mitigate these modes of injury.

PMID:21178995 | PMC:PMC3144654 | DOI:10.1038/eye.2010.149

Arch Ophthalmol. 2010 Jun;128(6):783-8. doi: 10.1001/archophthalmol.2010.80.

ABSTRACT

Francis Paddock (1814-1889), a graduate of Fairfield Medical College in western New York State, opened a general medicinal and surgical practice in the small town of Salem in Kenosha County, Wisconsin, between 1838 and 1839, where he lived and worked until his death a half century later. Two early volumes of his casebooks, spanning the years 1841 to 1852, came to light and are now analyzed from the standpoint of ophthalmic-related problems and their treatment. His life as a frontier physician and leading citizen of his community are documented in the context of 19th-century medicine in America and Wisconsin.

PMID:20547958 | DOI:10.1001/archophthalmol.2010.80

Ophthalmic Plast Reconstr Surg. 2010 May-Jun;26(3):208-10. doi: 10.1097/IOP.0b013e3181c952b6.

ABSTRACT

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.

PMID:20489549 | PMC:PMC2994249 | DOI:10.1097/IOP.0b013e3181c952b6

Arch Ophthalmol. 2010 Feb;128(2):212-22. doi: 10.1001/archophthalmol.2009.395.

ABSTRACT

OBJECTIVES: To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV).

METHODS: Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining.

RESULTS: Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels.

CONCLUSIONS: Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration.

CLINICAL RELEVANCE: The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

PMID:20142545 | PMC:PMC2820133 | DOI:10.1001/archophthalmol.2009.395