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We describe a 78-year-old woman with bilateral primary ciliary body melanomas. The tumours presented 6 months apart and were treated with iridocyclectomy. Histopathological examination revealed type B spindle cell melanomas. To our knowledge this is the first reported case of bilateral ciliary body melanomas.
A 3-year-old girl presented with a distorted pupil and decrease of visual acuity. A ciliary body mass at the superior-temporal quadrant could be seen at slit-lamp examination. Ultrasound biomicroscopy revealed a lesion with lobulated surface, arising at the ciliary body, composed of compact and cystic areas. An iridocyclectomy was performed but the tumour recurred after a few months. The eye was then enucleated. Histopathologic evaluation showed sheets and cords of proliferated medullary epithelium. Cystic spaces and Flexner-Wintersteiner rosettes were also seen. Those findings correlated well with ultrasound biomicroscopic images. The knowledge of echographic characteristics can significantly assist in the diagnosis of medulloepithelioma of the ciliary body.
Among 1352 eyes examined histopathologically, ciliary body epithelial cysts were found in 198 eyes. The cysts can be divided into 3 types: non-pigmented epithelial, pigmented epithelial and intra-epithelial cysts, the non-pigmented epithelial cysts being the most commonly seen. The former 2 types are formed by the proliferation of the inner and outer layer of the optic cup respectively and the formation of the latter one is related to the separation of the 2 layers of the cup. The cysts can be single or multiple, at most 14 non-pigmented ciliary epithelial cysts with 2 iris epithelial cysts being present in one eye. The incidence of ciliary epithelial cysts is as high as 14.6%. Because of the hidden position, clinical doctors seldom notice them. They can be misdiagnosed as melanoma, they can cause secondary glaucoma and localized cataract and they can be detached spontaneously. Therefore, clinical doctors ought to pay attention to this disease.
With the corrosion cast technique and electron microscopy, the major arterial circle of the iris, formed by the terminal branches of the medial and lateral long posterior ciliary arteries and of the anterior ciliary arteries, is shown not an anastomosed vascular ring but divided small branches of the arteries to supply the iris and ciliary body. The iris vessels demonstrate a radiate distribution of about 180-200 branches. The calibres of the iris arteries are homogeneous and measure about 50-120 microns. The branching portion of a precapillary arteriole begins with a constriction. The vessels of the ciliary processes account for more than half the volume of the ciliary body and have a rich capillary network of at least two layers. The draining veins are located on the surface and at the base of the ciliary body. There are 7-10 draining veins between two ciliary processes.
PURPOSE: Footpad injection of bacterial lipopolysaccharide (LPS) causes pronounced anterior uveitis in susceptible species and strains. Recent studies using wholemount techniques have demonstrated the presence of rich networks of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) and resident tissue macrophages in the iris and ciliary body. The aim of this investigation was to determine the immunophenotype and dynamics of the inflammatory cell infiltrate during LPS-induced anterior uveitis using the wholemount method and to examine the response of the resident tissue macrophages and DC to an acute inflammatory episode in the anterior segment. METHODS: Female Lewis rats (8 to 12 weeks old, n = 49) received a single footpad injection of 100 micrograms of LPS and were killed at various times up to 6 weeks after injection. The iris-ciliary body complex from each eye was removed intact and subdivided into segments and immunostained using a panel of monoclonal antibodies to a variety of immune cell types. RESULTS: The wholemount method clearly illustrates that during endotoxin-induced uveitis (EIU), the earliest cellular infiltrate includes small, round ED1+ mononuclear cells marginating in the iris vasculature approximately 2 hours after injection. Marginating Ox42+ polymorphonuclear leukocytes were detectable in the iris vessels approximately 4 to 6 hours after injection and were especially numerous in the ciliary body base approximately 24 hours after injection. The overall density of resident tissue macrophages (ED2+) remained largely unchanged in the course of EIU. In contrast, the total number of MHC class II-bearing (Ox6+) cells (putative dendritic cells) increased 30% in the first 6 hours and 200% by 72 hours. During the acute phase of the inflammatory response (up to 24 hours), the proportion of these cells with a dendritiform morphology decreased (93% to 50%). The number of T cells showed a biphasic response peaking at 4 to 6 hours and again at 24 hours (290 cells/mm2); however, their numbers had resumed normal low density (4 cells/mm2 to 25 cells/mm2) by 6 weeks. CONCLUSIONS: The results suggest that the neutrophilic infiltration in EIU occurs predominantly in the base of the ciliary body, whereas the monocytic and lymphocytic infiltrate occurs in the iris vasculature. Resident tissue macrophages do not undergo marked changes in density or morphology in the early course of the disease. Recruitment of T cells into the anterior segment in EIU may suggest a previously unsuspected role for these cells in the immunopathology of this disease. Changes in density and morphology of MHC class II+ DC in the iris, which persisted for at least 6 weeks, were interpreted as an increase in recruitment and migration of these cells that may serve to enhance the efficiency of immune surveillance in the anterior segment at crucial times of bacterial infection.
BACKGROUND AND OBJECTIVES: To evaluate the morphologic and functional effects of ciliary body photodynamic therapy (PDT) using phthalocyanine and a diode laser. MATERIALS AND METHODS: The upper half of the left eye ciliary body of 16 albino rabbits was irradiated transsclerally using a 670-nm diode laser (400 mW/cm2) after intravenous injection of phthalocyanine (6 mg/kg). The animals were observed for a maximum of 2 months by means of tonometry, biomicroscopy, and fundus examination. At the end of the follow-up period, they were killed and their eyes were prepared for light and electron microscopy. RESULTS: Transscleral PDT resulted in intraocular pressure (IOP) reduction in the treated eye, which lasted about 2 weeks. During this time, the treated eye had IOP values that were significantly lower than its baseline IOP values and the IOP values of the untreated eye (P < .05). One month after the procedure, the IOP had returned to baseline values. Histologic examination revealed vascular endothelial cell damage causing vascular thrombosis in the treated areas. The architecture of the two ciliary epithelium layers showed a significant abnormality. Disappearance of epithelial apical junction complexes and loss of the normal b-cytomembrane enfolding were observed in the course of electron microscopic examination. Large intercellular spaces between epithelial cells were noticed. All of these changes had subsided by the end of the second postoperative month. CONCLUSION: Transscleral phthalocyanine-mediated PDT with the parameters used in this experiment results in significant but temporary functional and morphologic alterations in the ciliary bodies of albino rabbits.
Five ciliary body membrane proteins were labeled when incubated with (adenylate-32P)NAD. Nitric oxide donors stimulated the labeling of 64, 40, and 29-30 kDa proteins and inhibited that of 58 and 56 kDa proteins. The greatest influence of nitric oxide was on the 40 kDa protein: a 17-fold stimulation. Western blotting and immunoprecipitation with specific antibodies identified this protein as the alpha-subunit of G(i-1). Studies with inhibitors showed that the protein was mono-ADP-ribosylated. Treatment of (32P)NAD-labeled G(i-1) with Hg and analysis of the released radioactive material showed that the protein was ADP-ribosylated on a cysteine residue.
The duration of the cell cycle in the sphincter pupillae and in the inner and outer neuroepithelia of the iris and ciliary body was studied. The four-day old rats were injected H3-thymidine and three-day old animals were administered H3-dopa to be processed for autoradiography. Cells of sphincter and of both neuroepithelia of the iris have the doubling time of 9.2--9.8 days, whereas the doubling time of cells of neuroepithelia of the ciliary body reaches 5.3--5.9 days. All pigmented epithelia of the iris-ciliary body complex synthesize melanin with the same intensity despite their specific differentiation. The most differentiated smooth muscle cells localized at the outer surface of the sphincter have almost half a melanin synthetic activity as compared with that of more deeply laying cells. Mitotic and H3-thymidine labelled cells were observed in all the areas of the sphincter. The data obtained were interpreted in terms of possible compatibility of both processes in smooth muscle cells of the iris; the synthesis of contractile proteins and the mitotic activity. The cell proliferation and differentiation of the structures in question were regarded as processes being regulated independentely at the stage studied.
Segments of whole ciliary body dissected from Dutch belted rabbits were incubated for 60 min at 36 degrees C in a 30 microM Ca2+ Ringer's. The inner limiting membrane with its adherent non-pigmented epithelium then was mechanically removed from the surface. The newly-exposed viable layer of pigmented cells was then loaded with the fluorescent probe 2'-7'-bis (carboxymethyl)-5(6) carboxyfluorescein by incubating the segments for 45 min at RT with the cell permeable acetoxymethoxy form of the dye. These loaded tissues were perfused in a flow-through chamber, mounted on the heated stage of a microscope equipped for quantitative epifluorescence, and the intracellular pH (pHi) of small groups of cells was derived from the ratio of emission intensities generated by excitations at 490 and 440 nm, respectively. In N[2-hydroxyethyl] piperazine-N"-[2 ethane sulfonic acid](Hepes)-buffered Ringer's the intracellular pH was 7.23 +/- 0.21 (+/- S.D., n = 20). Replacement of 28 mM Hepes by 28 mM HCO3-/5% CO2 led to a 0.14 +/- 0.04 increase in pHi. This increase required the presence of Na+ and Cl- and was inhibited by 0.2 mM diisothiocyanatostilbene-2-2'-disulfonic acid. These observations as well as characteristic pHi, responses to the removal or introduction of Na+ or Cl- indicated the presence in the pigmented cells of a Na(+)- and Cl(-)-dependent HCO3- transporter responsible for base uptake.
The clinical and detailed angiographical findings taken during the follow-up of 182 patients with tumors of the iris and the ciliary body reported. On the basis of different angiographic staining patterns, these tumors were divided into three groups. Group I: Clinically, as a rule darkly pigmented, slightly or nonprominent tumors, which do not take up fluorescein at all, i.e. no staining of the tumor of its surroundings during the whole angiogram. 107 patients with such a tumor type did not show any clinical or angiographical changes during several years of follow-up. Those tumors which were excised (4) proved to be nevi. We therefore believe this fluorescein pattern indicates a benign lesion so that examination every 6 months suffice. Group II: These are usually less pigmented and only slightly prominent and have their own vascular network. On fluorescein angiography there is dye leakage within the tumor and into the surrounding iris stroma as well as into the aqueous humor. Of a total of 52 cases 9 were excised via iridectomy or iridocyclectomy. Of these 5 were shown to be benign nevi, 4 however were diagnosed as malignant melanomas. We therefore classify this fluorescein angiographical pattern as belonging to potentially malignant tumors, needing frequent controls, i.e. at 3-month intervals. Group III: Clinically these tumors are usually darkly pigmented, extremely prominent and mostly situated in the peripheral iris, originating here or spreading forward from the ciliary body. They are usually vascularized and show - if the melanin content is not too dense - early mottled staining in the vicinity of the tumor. They furthermore always have a marginal central borderline fluorescence as a typical sign, often accompanied by dye leakage from normal iris vessels, representing so-called 'tumor iritis'. 18 tumors of this type were excised via iridocyclectomy or enucleation and all were shown to be malignant melanomas of the iris or the ciliary body on histopathological examination. This fluorescence pattern group of tumors should always be regarded as definitely malignant, and therefore need prompt surgical excision.
The aqueous humor of the eye is thought to be secreted by the epithelium of the ciliary body. This epithelium has been difficult to study, in part because of its complicated morphology. The authors attempted to circumvent this difficulty by growing the epithelial cells in tissue culture. A procedure is described for producing pure primary cultures of rabbit nonpigmented ciliary body epithelial cells. This procedure was used with whole-cell patch-clamp recording to characterize voltage-activated currents in the nonpigmented cells. These experiments show that most nonpigmented cells contain two kinds of currents: a rapidly activating and inactivating inward current, carried by Na+ and blocked by tetrodotoxin (TTX), and a more slowly activating and inactivating outward current, blocked by tetraethylammonium (TEA+), Ba2+, and 4-aminopyridine (4-AP) and presumably carried by K+. Both of these currents have been observed in freshly dissociated cells and in cultures up to 7 days old. The voltage-gated currents in ciliary body epithelial cells are remarkably similar to those of neurons and raise the possibility that these epithelial cells are capable of spike propagation.
Cattle affected by bovine Marfan's syndrome demonstrate most clinical features of the human disease, which is caused by mutations in the fibrillin-1 gene. Immunohistochemical and metabolic labeling studies in affected cattle have demonstrated abnormalities in fibrillin metabolism. Clinically identified ocular features of the bovine disease, which are similar to human Marfan's syndrome, are ectopia lentis, microspherophakia, and myopia. The purpose of this study was to compare the ocular pathology of the human and bovine diseases and to evaluate fibrillin-1 immunoreactivity in the extracellular matrix of explanted ciliary body cells from affected cattle. Eyes from affected cattle and unrelated normal cattle were examined grossly, and portions of the anterior uvea and ciliary zonule were examined by light and scanning electron microscopy. Portions of the ciliary zonular fibers were examined by transmission electron microscopy. The results were compared between affected animals and normal controls. Explanted ciliary body cells from two affected cattle and one unaffected cow were grown on chambered microscope slides, and expression of fibrillin-1 in the extracellular matrix was compared. Eyes of affected cattle were characterized by megaloglobus, increased circumlental distance, asymmetrical ciliary processes, intact but fragile zonular fibers, and ectopia lentis. Affected animals had moderately hypoplastic ciliary bodies, compact filtration angles, and long thin irises with decreased fibrous stroma. As shown by scanning electron microscopy, the zonular fibers of affected animals were wavy and loosely arranged, with abnormal sites of insertion on the lens capsule. The ciliary processes of affected animals had flattened or smooth surfaces. Explanted ciliary body cells from affected animals demonstrated decreased fibrillin immunoreactivity when compared with a normal control. The ocular pathology observed in bovine Marfan's syndrome is, in most respects, similar to that described for the human disease and will be a useful model for studies of in vivo evaluation of abnormal microfibrillar aggregation within ocular structures.
PURPOSE: To develop a means for noninvasive in vivo visualization of the ciliary processes using very-high-frequency (50 MHz) ultrasound and to develop quantitative morphologic descriptors that may relate to physiologic function. METHODS: The region of the ciliary body was scanned with very-high-frequency ultrasound, both in rabbits and in normal human subjects. Data were acquired in a series of planes so that the spacing between them was less than the beam width of the transducer in its focal plane. Three-dimensional perspective images were constructed, representing the anatomy of the angle region, including the ciliary processes. The automatically detected boundaries of the ciliary processes were analyzed to compute their periphery, area, shape factor, and fractal dimension. These measures were compared between the human and the rabbit eye and analyzed for periodicities related to the spacing of successive processes. RESULTS: Three-dimensional images allowed visualization of the radial arrangement of the processes. All biometric descriptors were significantly different between the rabbit and human eye and showed periodicities consistent with spacing between processes. CONCLUSIONS: The methods described in this report are sensitive descriptors of the state of the ciliary processes. These techniques may be of value in measurement of changes in the ciliary body associated with disease, medical therapy, and aging.
A 57-year-old man developed a ciliary body mass, clinically diagnosed as malignant melanoma of the ciliary body, that produced a cataract in the right eye. Treatment was cataract surgery with sclerouvectomy performed simultaneously. Pathohistologic examination revealed an acquired adenoma of the nonpigmented ciliary epithelium. The clinicopathologic features and treatment of this tumor are discussed.
Ciliary body detachment, hypotony, and visual loss developed within one month after an attempt to reopen a closed filtering bleb with YAG laser treatment. The patient was a 68-year-old black woman who had a previously functioning thermal sclerostomy. YAG laser energy delivered to the sclerosed filtering site ab interno was unsuccessful in restoring patency to the filtering site as judged by clinical examination. Because of hypotony, all glaucoma medications were discontinued. Resolution of the ciliary body detachment with return of vision and stable intraocular pressures occurred after three weeks of intensive topical and systemic corticosteroid treatment.
AIM: To evaluate the ciliary body and peripheral retina in degenerative retinoschisis associated with pars plana cysts using ultrasound biomicroscopy (UBM). METHODS: 18 eyes of 12 patients with degenerative retinoschisis associated with pars plana cysts were selected through binocular indirect ophthalmoscopy and Goldmann three mirror lens examination, both with scleral depression. These patients were studied in detail with UBM. RESULTS: Study of the ciliary body with UBM showed pars plana cysts of different size and uneven shape. In cross sections the morphology of pars plana cysts in detail and the close relation of the cysts with the oral region and the peripheral retina, where areas of cystoid degeneration and retinoschisis were present, were observed. In transverse sections three main morphological aspects of pars plana cysts could be differentiated ("isolated," "confluent," and "clustered" cysts). Furthermore, ultrabiomicroscopy allowed differential diagnosis between retinoschisis and associated retinal detachment in six eyes. CONCLUSIONS: The study of peripheral degenerative retinoschisis and pars plana cysts is possible in vivo by means of UBM, showing the detailed morphology of the lesions (not otherwise evident through ophthalmoscopic examination) and the close relation between pars plana cysts, cystoid degeneration, and peripheral retinoschisis.
Two benign tumors of the ciliary body diagnosed as neurogenic tumors by light microscopy were shown by electron microscopy to be composed of smooth muscle cells with unusual morphologic features. The light-microscopic appearance of a background fibrillary matrix imparting a "neural" appearance was the result of the interweaving of myriad cell processes filled with thin cytoplasmic filaments possessing fusiform densities. The perikaryon of the tumor cells was relatively free of filaments and displayed mitochondria and stacks of rough-surfaced endoplasmic reticulum suggestive of Nissl substance. The basis for these remarkable "hybrid" tumor cells--combining myogenic and neurogenic characteristics--is believed to reside in the neural crest origin of the smooth muscle of the ciliary body (mesectoderm). The histogenetic implications of mesectodermal tissue and the tumors that it spawns are discussed.
The pharmacology of prejunctional serotonin (5-HT) heteroreceptors that regulate the release of norepinephrine (NE) was studied in isolated bovine and human iris-ciliary bodies. The effect of exogenous 5-HT and various 5-HT receptor agonists was examined on the release of [3H]-norepinephrine ([3H]NE). Both 5-HT and m-chlorophenyl-biguanide (m-CPBG) caused enhancement in the field-stimulated release of [3H]NE from bovine tissues whereas 5-carboxamidotryptamine (5-CT) had no such effect. On the other hand, 8hydroxy-dipropylaminotetralin (8-OH-DPAT), caused a significant dose-related inhibition of evoked [3H]NE release. In human iris-ciliary bodies, 5-HT caused an inhibitory response on electrically-evoked [3H]NE release at low concentrations but produced an excitatory action at concentrations greater than 3 microM. To further confirm the nature of the prejunctional 5-HT heteroreceptors regulating [3H]NE release, effects of 5-HT3, 5-HT6 and 5-HT7 receptor antagonists were examined on a standard response to 5-HT. All antagonists examined caused a concentration-dependent inhibition of the response elicited by the standard 5-HT-induced response with the following rank order of potency (as measured by IC30 values): MDL-72222 >> SB-258719 > RO-04-690. We conclude that the excitatory prejunctional 5-HT heteroreceptors present in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype.