Intraocular tumors. A cytopathologic study

The cytologic characteristics and histopathologic correlates of common ocular tumors were examined using (1) cytologic and histologic specimens prepared from enucleated eyes with retinoblastoma and melanoma, (2) cytologic specimens prepared from clinically obtained intraocular fluids from eyes with lymphoma, metastatic adenocarcinoma and retinoblastoma and (3) cytologic specimens prepared from orbital aspirates and cerebrospinal fluids from a patient in whom retinoblastoma had spread to the orbit and central nervous system. Retinoblastoma cells occurred singly and in clusters and were associated with abundant necrotic debris and portions of capillaries with perivascular tumor infiltrates. Melanoma cells frequently had prominent nucleoli and variable amounts of fine cytoplasmic pigmentation and were found individually and in groups. Lymphoma cells were noncohesive, with scant cytoplasm. Metastatic intraocular adenocarcinoma cells had well-defined borders, multiple nucleoli and vacuolated cytoplasm. In general, the cellular morphology in the cytologic and tissue preparations of the intraocular tumors correlated well with each other. The findings suggest that common primary and metastatic intraocular tumors can be differentiated in cytologic preparations.     

Correlation study of benign cytomorphology and final clinical diagnosis

OBJECTIVE: To assess significance of cytologically benign vitreous samples and identify cellular patterns that may correspond to specific clinical entities. STUDY DESIGN: Vitreous fluids with "negative for malignancy" cytologic diagnosis were identified from pathology department records, cytologic slides reviewed and clinical and follow-up information obtained. RESULTS: Fifty-four cytologically benign samples were identified (1994-2004). The main indication for vitrectomy was confirmation of intraocular inflammatory process. Malignant process was included in the differential diagnoses of most samples. Macrophages or lymphocytes were the predominant cell types in 76% of cases. Most cases with macrophage or lymphocyte predominance were diagnosed as chronic uveitis or vitritis of unknown etiology. Infectious agents were identified in 7 cases with macrophage or lymphocyte predominance, 2 with abundant neutrophils and 1 with eosinophils. One had a diagnosis of malignant lymphoma, based on vitreous fluid from the opposite eye at another hospital. Three cases had blood only and 1 had lens fragments, both consistent with the diagnosis. CONCLUSION: Most cytologic features of benign vitreous fluids did not correspond to specific clinical entities. Abundant eosinophils suggested parasitic infection; the almost exclusive presence of blood indicated hemorrhage. Based on our study, negative predictive value of a benign vitreous sample is 98%.     

Target intraocular pressure in the management of glaucoma

Achievement of target intraocular pressure is the goal of every efficient antiglaucoma therapy. Target intraocular pressure is the level of intraocular pressure which is associated with minimal likelihood of visual field or optic nerve lesion, or an existing lesion progression due to elevated intraocular pressure. Results of large clinical studies which have offered some new concepts on target intraocular pressure in the management of glaucoma are reviewed. An association between the curve of intraocular pressure decrease and glaucoma progression was demonstrated in these studies. Generally, a lower value of target intraocular pressure implies better protection from the loss of vision and visual field impairment in glaucoma patients. In advanced glaucoma, the greatest possible reduction from the initial intraocular pressure should be attempted. A 20% reduction from the initial intraocular pressure or decrease to < 18 mmHg in advanced glaucoma has been recognized as a favorable strategy to reach target intraocular pressure. In normal tension glaucoma, a lower value of target intraocular pressure is associated with a slower disease progression. In patients with initial glaucoma, 25% reduction from the initial intraocular pressure will slow down the disease progression by 45%. The value of target intraocular pressure depends on the pretreatment level of intraocular pressure, optic nerve condition, glaucoma disease state, rate of glaucoma progression, patient's age, and other risk factors for the development of glaucoma.     

Glaucoma: An Extension of Various Chronic Neurodegenerative Disorders

The eyes are the window of the brain; various pathologies of the eyes can be explained on the basis of neurological disorders and vice versa. Today, our only approach for the management of glaucoma is intraocular pressure (IOP) reduction, whether by pharmacological or surgical methods. Available methods may effectively control IOP but fall short of stopping the progression of glaucoma. IOP is just one of the risk factors our therapy addresses, so we need to work towards shifting our approach towards addressing other factors involved in the etiopathogenesis of the disease. Pathogenesis of glaucoma at molecular level can be compared with that of common neurodegenerative diseases like Alzheimer’s and Parkinsonism. Targets for therapeutic intervention in chronic neurodegenerative diseases and glaucoma include apoptosis, axonal transport, free radical damage, role of polyunsaturated fatty acids, chaperones, gene regulation, etc. p38MAPK is a common pathway involved in all the neurodegenerative disease and glaucoma as well, and more research in this direction can be really beneficial for the development of novel diagnostic and therapeutic measures.     

Qualitative and quantitative analysis of peritoneal fluids from women with gynecologic diseases. Comparison of cytology and flow cytometry for the detection of malignancy in lavage and ascitic fluids

A prospective study was undertaken to compare flow cytometric (FCM) analysis to conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids (peritoneal lavages and ascitic fluids) from women with gynecologic diseases. The 94 peritoneal fluids analyzed came from 63 cancer patients (with epithelial ovarian carcinomas) and 31 control patients (with benign gynecologic diseases). The FCM DNA histograms were generated using propidium iodide as a DNA fluorochrome. Samples for cytologic analysis were stained with the standard May-Grünwald-Giemsa or Papanicolaou stains. Of the 94 samples, 90 were evaluable cytologically while 70 were suitable for FCM analysis. The sensitivities were 55% for FCM DNA analysis and 80% for cytologic analysis. FCM DNA analysis had a 30% false-positive rate; cytologic analysis produced no false-positive results. These results indicate that there is no advantage in employing FCM analysis instead of conventional cytologic evaluation for the detection of malignant cells in peritoneal fluids from gynecologic cases.     

Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage

In glaucoma, harmful intraocular pressure often contributes to retinal ganglion cell death. It is not clear, however, if intraocular pressure directly insults the retinal ganglion cell axon, the soma, or both. The pathways that mediate pressure-induced retinal ganglion cell death are poorly defined, and no molecules are known to be required. DBA/2J mice deficient in the proapoptotic molecule BCL2-associated X protein (BAX) were used to investigate the roles of BAX-mediated cell death pathways in glaucoma. Both Bax+/- and Bax-/- mice were protected from retinal ganglion cell death. In contrast, axonal degeneration was not prevented in either Bax+/- or Bax-/- mice. While BAX deficiency did not prevent axonal degeneration, it did slow axonal loss. Additionally, we compared the effects of BAX deficiency on the glaucoma to its effects on retinal ganglion cell death due to two insults that are proposed to participate in glaucoma. As in the glaucoma, BAX deficiency protected retinal ganglion cells after axon injury by optic nerve crush. However, it did not protect retinal ganglion cells from N-methyl-D-aspartate (NMDA)-induced excitotoxicity. BAX is required for retinal ganglion cell death in an inherited glaucoma; however, it is not required for retinal ganglion cell axon degeneration. This indicates that distinct somal and axonal degeneration pathways are active in this glaucoma. Finally, our data support a role for optic nerve injury but not for NMDA receptor-mediated excitotoxicity in this glaucoma. These findings indicate a need to understand axon-specific degeneration pathways in glaucoma, and they suggest that distinct somal and axonal degeneration pathways may need to be targeted to save vision.     

Introducing the shape of globe as a predisposing factor for glaucoma

Glaucoma is a common blinding disease worldwide with a number of risk factors such as intraocular pressure, myopia, gender, race and hyperopia. Here we introduce eyeball's shape as a predisposing factor for glaucoma. If the eyeball is a sphere, the stress distribution is homogenous. We assume the eyeball as a non sphere. Then, the distribution of stress will not be homogenous. Different individuals have different eyeball's shapes and different patterns of stress distribution in their eyes. So based on the eyeball's shape deviation from a sphere they will have different risks for glaucoma. The eyeball is routinely considered as a sphere, but some evidences show that the globe is not a sphere. Two empirical observations are consistent with the hypothesis. The first is that ethnicity and sex are established risk factors for glaucoma. On the other hand there are several morphological differences in the body structure among individuals. According to these anatomical differences, eye's shape is different among different races and between two sexes. Secondly, there are some conditions such as myopia and hyperopia in them the shape of the globe has been changed. These conditions are risk factors for glaucoma too. Glaucoma screening program for early detection of high risk individuals is very important. Current diagnostic procedures of glaucoma do not take the shape of eyeball into account. We suggest using eyeball's shape for early glaucoma detection. There are three other factors in addition to eyeball's shape, including thickness of the globe's wall, intraocular pressure, and inner radius that should be measured together for each individual and stress load should be calculated in different points of the globe. Then eyes with more stress load in site of injury are more prone for glaucoma. More accurate measurements of the factors which are contributing in stress value for each case, lead us toward better glaucoma screening.     

Role of the sympathetic nervous system in the pathogenesis of experimental glaucoma

It has been shown in experiments on rabbits that alpha-and beta-adrenoblockers, and lithium chloride solution exert different effect on intraocular tension of healthy animals with experimental glaucoma and transitory hypertension. The beta-blockker obsidan decreases the tension in experimental glaucoma. Pretreatment with the drug prevents the development of glaucoma. On the contrary, the alpha-blocker pirroxan promotes the development of glaucoma and does not elicit any hypotensive therapeutic effect. The drug-induced decrease in intraocular tension was recorded in healthy animals and in rabbits with transitory hypertensin of the eye. The hypotensive effect of lithium was noted only in the animals with experimental glaucoma. The role of alpha-and beta-adrenergic receiption in the pathogenesis of glaucoma is discussed.     

Corneal thickness in pseudoexfoliative glaucoma

Measurements of central cornea thickness (CCT) have a very important value in glaucoma patients; if the central cornea is thinner than it suggests, then the intraocular pressure is falsely low. This study compares the central cornea thickness between patients with pseudoexfoliative glaucoma, open angle glaucoma, angle closure glaucoma and control group. This study included 34 patients with pseudoexfoliative glaucoma, 31 patient with open angle laucoma, 28 patients with angle closure laucoma and 36 normal subjects in a control group. Patients in all groups and also normal subjects in control group had no other corneal disorders, no history of trauma, corneal surgery and were not patients with contacts lens use. Patients with pseudoexfoliative glaucoma and also patients with open angle glaucoma had significantly lower values of central cornea thickness compared with normal subjects in control group. Tomey EM 3000 is a non contact specular microscope which was used to measure central corneal thickness in this study. Pachymetry is an important method for diagnoses of glaucoma and for examination of the intraocular pressure in glaucoma patients, because values of the central corneal thickness affect the exact intraocular pressure readings.     

马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响

目的:探讨马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响。方法:选取2015年1月-2016年5月在我院接受治疗的原发性开角型青光眼患者84例,其中给予马来酸噻吗洛尔眼液治疗的42例记为对照组,给予拉坦前列素眼液联合马来酸噻吗洛尔眼液治疗的42例记为观察组,两组均治疗6个月。对比两组患者治疗过程中的眼压变化情况,并对比两组患者的临床总有效率、药物依从性和并发症情况。结果:观察组治疗2、4、6个月后的眼压均显著低于对照组(P0.05),观察组患者治疗6个月后与治疗前的眼压差值大于对照组(P0.05)。两组患者治疗2、4、6个月后的眼压呈下降趋势,两两比较差异均有统计学意义(P0.05)。观察组的临床总有效率95.24%显著高于对照组的80.95%(P0.05)。两组患者在治疗过程中结膜充血、眼内异物感、眼睛疼痛、视力模糊、味觉异常以及总并发症发生率对比差异不显著(P0.05)。观察组患者的药物依从性比例显著低于对照组(P0.05)。结论:马来酸噻吗洛尔眼液联合拉坦前列素眼液治疗原发性开角型青光眼患者具有较好的临床疗效,可显著降低患者眼压,同时具有较好的安全性,但药物依从性较差。     

Amyloid fibril formation by the glaucoma-associated olfactomedin domain of myocilin

Myocilin is a protein found in the extracellular matrix of trabecular meshwork tissue, the anatomical region of the eye involved in regulating intraocular pressure. Wild-type (WT) myocilin has been associated with steroid-induced glaucoma, and variants of myocilin have been linked to early-onset inherited glaucoma. Elevated levels and aggregation of myocilin hasten increased intraocular pressure and glaucoma-characteristic vision loss due to irreversible damage to the optic nerve. In spite of reports on the intracellular accumulation of mutant and WT myocilin in vitro, cell culture, and model organisms, these aggregates have not been structurally characterized. In this work, we provide biophysical evidence for the hallmarks of amyloid fibrils in aggregated forms of WT and mutant myocilin localized to the C-terminal olfactomedin (OLF) domain. These fibrils are grown under a variety of conditions in a nucleation-dependent and self-propagating manner. Protofibrillar oligomers and mature amyloid fibrils are observed in vitro. Full-length mutant myocilin expressed in mammalian cells forms intracellular amyloid-containing aggregates as well. Taken together, this work provides new insights into and raises new questions about the molecular properties of the highly conserved OLF domain, and suggests a novel protein-based hypothesis for glaucoma pathogenesis for further testing in a clinical setting.     

不同术式治疗新生血管性青光眼的疗效比较

目的：比较不同手术方法治疗新生血管性青光眼（neovascular glaucoma,NVG）的疗效。方法：对接受不同术式治疗的57例57只眼NVG的临床资料进行回顾性分析,其中行单纯睫状体冷凝术20例（A组）,改良小梁切除术15例（B组）,引流阀植入术联合全视网膜光凝术22例（c组）。比较各组患者手术前后主观眼痛症状、眼压及视力变化情况,并随访3～6个月。结果：A组患者出院时的平均眼压为（28．13＋4．83）mmHg,B组为（19．24±5．48）mmHg,C组为（21．22±4．76）mmHg。随访期间,术后A组9例眼压正常,手术成功率45％;B组11例眼压正常,手术成功率73．3％;C组13例眼压正常,手术成功率57．1％。B组手术成功率最高,A组最低。结论：三种手术方法均可不同程度降低新生血管性青光眼的眼压。单纯睫状体冷凝术后眼压控制效果欠佳,有视力眼不宜采用此种手术方式;改良小梁切除术是治疗新生血管性青光眼安全、有效、经济的手术方式;引流阀植入术联合全视网膜光凝术费用较高。     

1α,25-Dihydroxyvitamin D(3) and its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (2MD), suppress intraocular pressure in non-human primates

Ocular hypertension is the greatest known risk factor for glaucoma that affects an estimated 70 million people worldwide. Lowering intraocular pressure (IOP) remains the mainstay of therapy in the management of glaucoma. By means of microarray analysis, we have discovered that 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)) regulates genes that are known to be involved in the determination of intraocular pressure (IOP). Topical administration of 1α,25-(OH)(2)D(3) or its analog, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D(3) (2MD), markedly reduces IOP in non-human primates. The reduction in IOP is not the result of reduced aqueous humor formation, while a 35% increase in aqueous humor drainage by 1α,25-(OH)(2)D(3) was found but this increase did not achieve significance. Nevertheless, our results suggest that 1α,25-(OH)(2)D(3), or an analog thereof, may present a new approach to the treatment of glaucoma.     

The molecular dynamics of hyaluronates in solution.

The dynamic properties of hyaluronate solutions are discussed with relevance to some problems in sensory physiology (mechanoelectrical transduction), renal physiology, interstitial fluid regulation, and especially to the causes of open-angle glaucoma. With respect to the last problem: as recent biochemical evidence indicates that the hyaloid membrane does not exist, it now seems worthwhile to consider the increase in intraocular pressure present in the eye with glaucoma to be due--at least in the open-angle case--to a change in the specific gravity and hydrophilic nature of the hyaluronic acid in the vitreous body in particular, as well as in the trabecular meshwork. Densimetric experimental evidence indicates that the hyaluronate system could, indeed, produce the pressure changes seen in glaucoma, if intraocular pH changed but slightly. A hypothesis concerning the effect of acetazol amide on intraocular pressure is also presented.     

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Diagnostic cytologic features of an epididymal melanotic neuroectodermal tumor of infancy present in scrotal fluid: a case report

BACKGROUND: The cytologic features of melanotic neuroectodermal tumor of infancy (MNTI) have been described in rare cases only, and these reports have been based solely on direct smears obtained from aspirated tumor material or from touch preparations of resected tumors. CASE: We report, to our knowledge, the first documented case of an epididymal MNTI diagnosed from aspirated hydrocele fluid processed using the ThinPrep system (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). CONCLUSION: Based on a 15 year retrospective review of scrotal fluids submitted for cytologic evaluation to our laboratory, MNTI represented the sole neoplasm that was represented in the fluid and could be specifically diagnosed. Compared to the direct smear evaluation in our case and other published reports, the ThinPrep method enables the recognition of both neuroblast-like cells and larger melanin-containing epithelial cells in scrotal fluid, thereby aiding in the specific diagnosis of MNTI and minimizing the risk of misdiagnosing this tumor as a more aggressive neoplasm.     

Hemoglobin crystals in fluid specimens from confined body spaces

Hemoglobin crystals phagocytized by polymorphonuclear leukocytes were seen in cytologic preparations of a cerebrospinal fluid and two pleural fluids. In the last two cases, the crystals were seen within erythrocytes and also free in the background. Intraerythrocytic crystallization of hemoglobin is the result of polymerization of the hemoglobin molecules; it occurs in peripheral blood in certain hemoglobinopathies, being more pronounced in hemoglobin C disease. In our three cases, in which the crystallization occurred not in peripheral blood but in fluids of confined body spaces, there was no clinical evidence of hemoglobinopathy and blood hemoglobin electrophoresis performed in one of the cases revealed normal hemoglobin. Under laboratory conditions, we produced intraerythrocytic crystallization of hemoglobin in hemorrhagic pleural fluid specimens by subjecting them to agents that induced decreased oxygen concentration and osmotic dehydration of the cells. We suggest that similar processes operative in fluid accumulated in confined body spaces produce crystallization of the hemoglobin of extravasated red blood cells in the absence of hemoglobinopathy.     

Corneal thickness in congenital glaucoma

Central corneal thickness is very important measurement in glaucoma treatment because it influences the eye pressure measurements. A thinner cornea gives us artifactually lower intraocular pressure and a thicker cornea gives higher intraocular pressure reading, so it has to be corrected in both cases. The aim of this study is to compare central corneal thickness between congenital glaucoma patients and normal subjects. Prospective study included 27 patients with congenital glaucoma and 35 patients in control group. First group was subdivided in two subgroups: A--8 earlier operated patients, B--19 patients treated with topic therapy. Patients had no other corneal disorders, history of trauma, corneal surgery and they were not contact lens wearers. Measurements were performed by specular microscope Tomey EM 3000 on central corneas. This study showed that patients with congenital glaucoma have lower central corneal thickness than normal subjects. Also, the study showed that antiglaucomatous operation doesn't influence central corneal thickness. Central corneal thickness need to be a routine part of examination measurements because of need to correct intraocular pressure according to it, but also the thinner corneas values can suggest congenital glaucoma diagnosis beside the other parameters.     

不同术式治疗新生血管性青光眼的疗效比较

目的:比较不同手术方法治疗新生血管性青光眼(neovascular glaucoma,NVG)的疗效。方法:对接受不同术式治疗的57例57只眼NVG的临床资料进行回顾性分析,其中行单纯睫状体冷凝术20例(A组),改良小梁切除术15例(B组),引流阀植入术联合全视网膜光凝术22例(C组)。比较各组患者手术前后主观眼痛症状、眼压及视力变化情况,并随访3~6个月。结果:A组患者出院时的平均眼压为(28.13±4.83)mmHg,B组为(19.24±5.48)mmHg,C组为(21.22±4.76)mmHg。随访期间,术后A组9例眼压正常,手术成功率45%;B组11例眼压正常,手术成功率73.3%;C组13例眼压正常,手术成功率57.1%。B组手术成功率最高,A组最低。结论:三种手术方法均可不同程度降低新生血管性青光眼的眼压。单纯睫状体冷凝术后眼压控制效果欠佳,有视力眼不宜采用此种手术方式;改良小梁切除术是治疗新生血管性青光眼安全、有效、经济的手术方式;引流阀植入术联合全视网膜光凝术费用较高。     

兔先天性青光眼的临床研究

目的 总结兔先天性青光眼的临床特点。方法 对先天性青光眼兔和正常兔进行临床观察,研究其在眼压、眼球结构、视功能方面的变化。结果 青光眼兔的眼压明显升高,角膜直径变大,前房变深,眼轴变长,房角变宽,眼底视乳头损害明显,视觉诱发电位明显异常。结论 兔先天性青光眼的房水排泄障碍部位可能在小梁,兔眼球壁对高眼压的耐受力弱,在高眼压下容易出现眼球扩张,视功能损害。