Cilioretinal artery occlusion and anterior ischemic optic neuropathy as the initial presentation in a child female carrier of Fabry disease.

PURPOSE: To report the youngest female carrier of Fabry disease, complicated by cilioretinal artery occlusion and anterior ischemic optic neuropathy (AION). METHODS: Case report. RESULTS: An 11-year-old girl was referred to our clinic with painless, acute loss of vision in her right eye. Posterior segment examination and fluorescein angiography revealed cilioretinal artery occlusion and AION. Systemic evaluations were unremarkable, except for a low blood α-galactosidase A enzyme level of 242.27 pmol/spot*20 h (reference range: 450-2000 pmol/spot*20 h). The patient was diagnosed with female carrier of Fabry disease. CONCLUSION: Retinal vascular occlusions are rare in childhood, and Fabry disease may present with retinal vascular occlusion. Ophthalmological examinations may be contributing for early detection of the disease. To the best of our knowledge, this is the first report of a child female carrier of Fabry disease, complicated by cilioretinal artery occlusion and AION.

Radiation induced violations of blood circulation in the ciliary body and changes of the anterior chamber angle in the pathogenesis of glaucoma in clean up workers of the Chornobyl NPP accident and residents of contaminated areas. / RADITsIY̆NO INDUKOVANI PORUShENNIa KROVOOBIGU V TsILIARNOMU TILI TA ZMINY KUTA PEREDN'OI KAMERY OKA V PATOGENEZI GLAUKOMY V UChASNYKIV AVARIY̆NYKh ROBIT NA ChORNOBYL'S'KIY̆ AES I MEShKANTsIV ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: Estimate changes blood filling of the ciliary body and changes of the anterior chamber angle; study their influence to glaucoma pathogenesis in irradiated persons. MATERIALS AND METHODS: Used the results of a randomly selected group survey of 41 clean up workers of the Chornobyl NPP accident (clean up workers), and 18 inhabitants of the zone of guaranteed voluntary resettlement; age at the time of the survey was 45-50 years. The control group consisted of 41 persons of the same age had not radiation exposure. State of the anterior chamber angle studied by gonioscopy, which was conducted 35 clean up workers and 35 persons of the control group. Changes of the blood circulation in the ciliary body examine by the ophtalmoreog raphy, what was done on 12 eyes of 6 clean up workers, control was 12 eyes of 6 persons had not radiation exposure. RESULTS: Detection revealed of the blood circulation in the ciliary body in all clean up workers, reography coefficient was probably lower (p < 0.05), than in the control group. The research of the state of the anterior chamber angle revealed a higher relative risk of appearance of involution changes of the anterior chamber angle in clean up work ers of ChNPP accident, in comparison with the control group was 3.5 (1.27; 9.5) χ2 = 7.48, p = 0.031. The same changes are characteristic for inhabitants of radiation polluted territories. CONCLUSIONS: Influence ionizing radiation causes a blood circulation decrease in the ciliary body and development changes of the angle of the anterior chamber. Presence of these changes can explain the features of the pathogene sis of glaucoma in irradiated late manifestation and, at the same time, severe course.

The effects of VEGF-A-inhibitors aflibercept and ranibizumab on the ciliary body and iris of monkeys.

PURPOSE: To investigate the effects of intravitreal ranibizumab (Lucentis®) and aflibercept (Eylea®) on the ciliary body and the iris of 12 cynomolgus monkeys with regard to the fenestrations of their blood vessels. MATERIALS AND METHODS: Structural changes in the ciliary body and in the iris were investigated with light, fluorescent, and transmission electron microscopy (TEM). The latter was used to specifically quantify fenestrations of the endothelium of blood vessels after treatment with aflibercept and ranibizumab. Each of the two ciliary bodies treated with aflibercept and the two treated with ranibizumab and their controls were examined after 1 and 7 days respectively. Ophthalmological investigations including funduscopy and intraocular pressure measurements were also applied. RESULTS: Ophthalmological investigations did not reveal any changes within the groups. Both drugs reduced the VEGF concentration in the ciliary body pigmented epithelium. The structure of the ciliary body was not influenced, while the posterior pigmented epithelium of the iris showed vacuoles after aflibercept treatment. Ranibizumab was mainly concentrated on the surface layer of the ciliary epithelium, in the blood vessel walls and the lumen of some of the blood vessels, and in the cells of the epithelium of the ciliary body. Aflibercept was more concentrated in the stroma and not in the cells of the epithelium, but as with ranibizumab, also in the blood vessel walls and some of their lumina, and again on the surface layer of the epithelium. Both aflibercept-and ranibizumab-treated eyes showed a decreased number of fenestrations of the capillaries in the ciliary body compared to the untreated controls. On day 1 and day 7, aflibercept had fewer fenestrations than the ranibizumab samples of the same day. CONCLUSIONS: Both aflibercept and ranibizumab were found to reach the blood vessel walls of the ciliary body, and effectively reduced their fenestrations. Aflibercept might eliminate VEGF to a greater extent, possibly due to a higher elimination of fenestrations in a shorter time. Moreover, the vacuoles found in the iris need further research, in order to evaluate whether they carry a possible pathological potential.

Study of microcirculation of the ocular ciliary body in experimental kidney disease.

We studied disorders in ciliary body microcirculation in experimental chronic glomerulonephritis with tubulointerstitial nephritis and evaluated the hemodynamic effects of low-frequency pulsed electromagnetic field in this pathology. Laser Doppler flowmetry demonstrated vasospasm with reduced nutrient blood fl ow in the ciliary body of animals with experimental chronic glomerulonephritis with tubulointerstitial nephritis. The exposure to low-frequency pulsed electromagnetic field using developed technology will lead to significant reduction of the vascular tone and improve arterial blood supply to the microcirculatory bed.

Expression of the primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in endothelial and epithelial cell junctions in the eye.

PURPOSE: The role of the recently identified primary angle closure glaucoma (PACG) susceptibility gene, pleckstrin homology domain containing, family A member 7 (PLEKHA7), in PACG is unknown. PLEKHA7 associates with apical junctional complexes (AJCs) and is thus implicated in paracellular fluid regulation. We aimed to determine PLEKHA7's localization in the eye and its association with AJCs to elucidate its potential role in PACG. METHODS: Total RNA from ocular tissues was isolated and analyzed by real-time PCR. Frozen and paraffin-embedded human globes were sectioned and used for immunohistochemistry and immunofluorescence analysis. RESULTS: Specific PLEKHA7 expression was found in the muscles, vascular endothelium, and epithelium of the iris, ciliary body and ciliary processes, trabecular meshwork (TM), and choroid. PLEKHA7 expression in musculature and vascular endothelium was confirmed with smooth muscle marker, SMA, and endothelium marker, PECAM-1, respectively. At the above sites, PLEKHA7 colocalization was seen with adherens junction markers (E-cadherin and ß-catenin) and tight junction markers (ZO-1). CONCLUSIONS: Specific localization of PLEKHA7 was found within PACG-related structures (iris, ciliary body, and choroid) and blood-aqueous barrier (BAB) structures (posterior iris epithelium, nonpigmented ciliary epithelium, iris and ciliary body microvasculature). The association of PLEKHA7 with AJCs in the eye suggests a potential role for PLEKHA7 in PACG via fluidic regulation. Novel expression of PLEKHA7 was also seen in the ocular smooth muscles and vascular endothelia.

Ciliary epithelium: an underevaluated target for therapeutic regeneration.

The purpose of stem cells in various organs of vertebrates is to replenish dying cells or to replace damaged tissues. However, a few organs have reasonable, while others have very limited regenerative, capacity. Until the last two decades, the organs such as brain, heart, and kidneys were known to lack regenerative capacity for lack of resident stem cell population. However, with advancement of techniques and an increase in scientific communication, new discoveries have brought novel concepts and data to discover and manipulate these valuable resources. Much focus has been devoted to understanding the regulation and maintenance of these stem cells. We discuss the preclinical data emerging from retino-vascular interactions useful in the exploitation of ciliary epithelium-derived stem cells for therapeutic regeneration.

Miniaturized high-intensity focused ultrasound device in patients with glaucoma: a clinical pilot study.

PURPOSE: To evaluate the relative safety and potential efficacy of high-intensity focused ultrasound cyclocoagulation by a miniaturized annular device containing six piezoceramic transducers in patients with refractory glaucoma. METHODS: This was a three-center prospective interventional pilot study. Twelve eyes of 12 patients with refractory glaucoma were insonified using a ring-shaped probe containing six miniaturized high-frequency transducers operating at 21 MHz. Ultrasound biomicroscopy (UBM) and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, 1 month, and 3 months after the procedure. Additional visits were performed 6 and 12 months after the procedure. RESULTS: Intraocular pressure was significantly reduced (P < 0.01) from a mean preoperative value of 37.9 ± 10.7 mm Hg to a mean postoperative value of 27.3 ± 12.4, 25.2 ± 11.3, 25.2 ± 7.7, 24.8 ± 9.8, and 26.3 ± 5.1 mm Hg at 1 day, 1 week, 1 month, 3 months, and 6 months, respectively, and to a mean value of 24.7 ± 8.5 at the last follow-up visit. No major intraoperative or postoperative complications occurred. Minor postoperative corneal complications developed in four patients with previous corneal abnormalities: superficial punctate keratitis (n = 3) and central superficial corneal ulceration (n = 1). UBM showed cystic involution of the ciliary body in 9 of the 12 eyes and a suprachoroidal fluid space in 8 of the 12 eyes. CONCLUSIONS: Ultrasonic circular cyclocoagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing six piezoceramic transducers seems to be an effective and well-tolerated method to reduce intraocular pressure in patients with refractory glaucoma.

Angiographic changes in iris and iridocorneal angle neovascularization after intravitreal bevacizumab injection.

OBJECTIVE: To evaluate the effects of the intravitreal (IV) injection of bevacizumab on anterior segment neovascularization using anterior segment angiography. METHODS: We observed 1 eye with iris and iridocorneal angle neovascularization and 3 with neovascular glaucoma from 4 patients with diabetic retinopathy in 3 eyes and central retinal vein occlusion in 1 eye. Two healthy eyes from 2 other patients served as control eyes. Three eyes, including 1 normal eye, were examined by iris angiography; the other eyes underwent iridocorneal angle angiography with fluorescein (FA) and indocyanine green (IA) using a Heidelberg Retina Angiograph 2. After angiography, 4 eyes with neovascularization were treated with IV bevacizumab (1.25 mg per 0.05 mL) and underwent angiography once more 4 to 6 days after treatment. RESULTS: Iris angiography with indocyanine green revealed many iris vessels, but not dye leaking, in both normal and glaucomatous eyes, and the angiography with fluorescein showed intensive vessel leakage in the iris as well as iridocorneal angle neovascularization, but not in normal eyes. Angle angiography revealed vessel structures with indocyanine green and intensive leakage with fluorescein in the iris and showed iridocorneal angle neovascularization and neovascular glaucoma, whereas no vessel structures appeared with IA or FA in the normal eye. After IV bevacizumab injection in eyes with neovascularization, the vascular structure did not change with IA, but dye leakage remarkably decreased with FA in the iris and angle. However, newly formed vessels in the iris and iridocorneal angle seemed to disappear on slitlamp examination. CONCLUSION: Intravitreal injection of bevacizumab effectively reduces vascular permeability, whereas newly formed vessels are still present in the iris and iridocorneal angle.

In vivo evidence of hypotrophic ciliary body in ocular ischemic syndrome by ultrasound biomicroscopy.

In ocular ischemic syndrome, the ischemic condition is due to markedly reduced blood flow and increased vascular resistance of retrobulbar circulation, as in the central retina and posterior ciliary arteries. Chronic hypoxia affects even the iris and ciliary body. The hypoperfusion of the ciliary body leads to a relative hypotony, presumably related to decreased aqueous humor production. Histopathologic study has demonstrated ciliary body atrophy on an ischemic basis. The authors used ultrasound biomicroscopy to demonstrate in vivo the hypotrophic condition of the ciliary body in ocular ischemic syndrome.

Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model.

PURPOSE: To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes. METHODS: A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Verteporfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm2 and fluence of 100 J/cm2. Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT. RESULTS: In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes. CONCLUSIONS: Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.

Ciliary tissue transplantation in the rabbit.

Irreversible damage of the ciliary body can be responsible for prolonged ocular hypotony and phthisis bulbi, which, currently, cannot be treated. The aim of this study was to achieve survival of morphologically normal ciliary tissue (CT) transplants in the anterior chamber of a rabbit's eye. Outbred female New Zealand albino rabbits received CT allografts, which were placed on to the surface of the host iris. We evaluated the influence of ciclosporin (CsA), VEGF and donor perfusion on graft survival. Operated eyes were assessed clinically and histologically, and revascularization of the grafts was determined by fluorescein angiography. All grafts became dark and ischemic during the first five to seven days after transplantation. Reperfusion of the grafted tissue was complete at approximately ten days after transplantation. In untreated animals, transplants became infiltrated by inflammatory cells, which led to destruction of the tissue. This was prevented by systemic use of CsA. Transplants treated with VEGF prior to transplantation had fewer ischemic areas but epithelial cell survival was not improved. Whole body donor perfusion prior to preparation of the grafts resulted in less inflammation and, histologically, in a better quantity and quality of the epithelial cells in the CT transplants. Ciliary tissue can be successfully transplanted but the ciliary epithelium suffers from ischemia and in untreated animals the whole transplant is rejected in the classical fashion. If the donor is perfused and the host immunosuppressed, histologically normal ciliary epithelium can be preserved together with rapid revascularization, minimal inflammation and good survival of the transplant, although fibrosis continued to occur during the two months after transplantation.

[The effect of preventing anterior segment ischemia by preservation of anterior ciliary vessels in rabbit].

OBJECTIVE: To investigate the effect of preserving anterior ciliary vessels (ACVs) on the prevention of anterior segment ischemia syndrome (ASI) during the surgery of extraocular muscles. METHODS: Thirty-two adult New Zealand white rabbits were randomly divided into four groups. ACVs of the right eyes were preserved among all of the rabbits, and were cut off in all of the left eyes. Group A: internal and external recti were cut off in two eyes; Group B: superior and inferior recti were cut off in two eyes; Group C: internal, external and superior or inferior recti were cut off in two eyes; Group D: all of the recti were cut off in two eyes. All rabbits were observed under slit microscope. The intraocular pressure (IOP), the total protein and lactic acid in the aqueous humor were recorded preoperatively and postoperatively. Eyes were enucleated at the forth week postoperatively to obtain the iris and the ciliary body for histopathologic study and electron microscopy. RESULTS: No signs of ASI were observed in the right eyes of all four groups under the slit lamp and under the light and election microscopes. The IOP and levels of ingredients of aqueous humor (total protein and lactic acid) showed no difference between preoperative and postoperative interval. No obvious ASI was observed in the left eyes of group A. Mild reactions of ASI were observed in the left eyes of group B. Moderate to severe reactions of ASI were observed in the left eyes in group C and group D. The IOP reduced from (17.21 +/- 3.76) mm Hg (1 mm Hg = 0.133 kPa) preoperatively to (14.48 +/- 3.36) mm Hg postoperatively in group C (P < 0.05); and from (16.68 +/- 2.33) mm Hg reduced to(3.17 +/- 0.92) mm Hg in group D. (P < 0.05). The level of total protein and lactic acid in the aqueous humor increased from (505.3 +/- 5.0) mg/L and (7.54 +/- 0.47) g/L preoperatively to (811.9 +/- 44.4) mg/L and (11.00 +/- 3.59) g/L postoperatively in group C, respectively (P < 0.05). In group D, the level of total protein and lactic acid in the aqueous humor increased from (504.6 +/- 4.1) mg/L and (7.17 +/- 1.44) g/L preoperatively to (1025. 8 +/- 78.3) mg/L, (8.23 +/- 1.68) g/L postoperatively, respectively (P < 0.05). There were various histopathological changes under the light and electron microscope in groups C and D. While no obvious ischemic changes were observed in group A. CONCLUSION: Two vertical muscles cut off at one eye simultaneously would produce mild reactions of ischemia, while three or more muscles cut off simultaneously could obstruct blood flow in eyes and induce ASI. Preservation of the ACVs could avoid the occurrence of ASI.

Optociliary venous anastomosis after radial optic neurotomy for central retinal vein occlusion.

Radial optic neurotomy has been shown to be beneficial for the treatment of central retinal vein occlusion. Two patients developed optociliary venous anastomosis after radial optic neurotomy for central retinal vein occlusion with improvement in vision and clinical appearance. Optociliary venous anastomosis may portend a favorable prognosis.

Distribution and organization of the nerve fiber and ganglion cells of the human choroid.

Antibodies to the 68, 160 and 200 kD of the neurofilament triplets were used to study the distribution and organization of neuronal structures in the human choroid. Choroidal axons were observed in the suprachoroid and vascular laminae but absent from the choriocapillary layer. Most axons were situated in the suprachoroid. In this layer, there were band-like bundles. The two thickest band-like bundles could constitute the long ciliary nerve, while the rest could constitute short ciliary nerves. These bundles ran through the suprachoroid, branching out on the suprachoroid and the vascular laminae until they reached the ciliary body. In the submacular area of the suprachoroid, the branches of the band-like bundles were so intermingled that they looked like a meshwork. In the vascular layer, the large vessels and their primary branches were accompanied by paravascular axons. Some paravascular axons penetrated the medium-caliber vessel layer and in the submacular area interwove to form a network parallel to the arteriole walls. In addition, perivascular axons were revealed by antibodies to neuropeptides. Choroidal ganglion cells were more numerous in the central choroid, specifically in a circumferential area corresponding to the entrance of the short posterior ciliary arteries and their primary branches, and in the vicinity of the submacular area. These cells presented bipolar and multipolar morphology. The high concentration of innervation in the central human choroid could be necessary to maintain strict blood flow in this zone; thus if required, these neuron structures could induce early vasodilation reflexes at the entrance of the choroidal blood vessels to increase the blood flow.

Neovascularization in the anterior segment of the rabbit eye by experimental anterior ischemia.

PURPOSE: To investigate the effects of anterior ischemia accompanied by neither retinal nor choroidal ischemia on the anterior segment of the eye. METHODS: Both long posterior ciliary arteries in the right eye of 14 rabbits were directly cauterized with an electric coagulator. The eyes were enucleated 1, 2, 4, 7, 9 or 14 days after cauterization, then fixed with 4% paraformaldehyde. Semi-thin sections were studied by light microscopy. Several sections were stained with Griffonia simplicifolia lectin, which bound specifically to mammalian vascular endothelium. Other specimens were examined immunohistochemically for vascular endothelial growth factor (VEGF) protein. The tissue specimens of the first postoperative day were studied for expression of VEGF mRNA by in situ hybridization. RESULTS: Atrophy of the iris and ciliary body was seen after the second postoperative day. Corneal neovascularization appeared after 7 days. Neovascularization on the anterior surface of the iris and in the trabecular meshwork was detected after the ninth postoperative day. The proliferative tissues with newly formed vessels obstructed the iridocorneal angle 14 days after the treatment. There was no histological change in either the retina or choroid. Immunohistochemically, VEGF protein was detected in the epithelial and vascular cells of the iris on the first and fourth postoperative day. Expression of VEGF mRNA was detected in the epithelial cells of the ciliary body on the day following the treatment. CONCLUSIONS: Anterior segment ischemia, when unaccompanied by retinal ischemia, causes neovascularization in the cornea, iris and trabecular tissue.

Microcirculation patterns other than loops and networks in choroidal and ciliary body melanomas.

PURPOSE: To provide ophthalmologists and pathologists with expanded criteria for separating patients at high risk of metastatic melanoma from those at low risk on the basis of microcirculation patterns in choroidal and ciliary body melanomas. DESIGN: Tissue culture studies and observational case series. PARTICIPANTS: The pattern-forming ability of four uveal melanoma cell lines of varying degrees of aggressive behavior was studied in vitro. Histologic sections of 234 eyes removed for choroidal or ciliary body melanoma were studied for the presence of microcirculation patterns. METHODS: The study was divided into two phases: the study of histologic sections of eyes removed for choroidal and ciliary body melanomas and observations on the in vitro behavior of cultured melanoma cells of varying degrees of invasive behavior. The presence or absence of each of nine microcirculation patterns was recorded from tissue sections, and interrelationships between different patterns were explored statistically. In vitro reconstitution of patterns and a study of the interrelationships of patterns in histologic sections was carried out. In the in vitro studies, uveal melanoma cell lines of varying degrees of aggressive potential were cultured to observe the development of architectural patterns other than loops and networks. MAIN OUTCOME MEASURES: In histologic studies, the outcome measure was the conditional probability of detecting loops or networks given the presence or absence of other patterns positive for periodic acid-SCHIFF: For tissue culture studies, the outcome measure was either the development or lack of development of patterns of different shapes in vitro. RESULTS: Histologic studies disclosed that given the presence of arcs without or with branching in a tissue section, it is likely that loops or networks will be detected in the same section plane, suggesting that the production of these patterns by aggressive tumor cells reflects a spectrum of architectural potential. In vitro studies confirmed this hypothesis by revealing that highly aggressive and metastatic uveal melanoma cell lines, but not poorly aggressive tumor cell lines, generated parallel channels with and without crosslinking and arcs with and without branching as well as loops and networks. CONCLUSIONS: The criteria for separating patients into low- and high-risk categories for metastasis from uveal melanoma should be expanded to include patterns other than loops or networks. In both the pathology laboratory as well as in a clinical setting, the detection of arcs or arcs with branching and parallel channels should prompt a careful search for loops and networks and for crosslinking parallel channels, respectively.

Ultrasound biomicroscopy in a case of anterior hyaloidal fibrovascular proliferation.

The authors describe the use of ultrasound biomicroscopy for the diagnosis and preoperative evaluation of anterior hyaloidal fibrovascular proliferation (AHFVP). Ultrasound biomicroscopy was performed on a 62-year-old man who presented after diabetic vitrectomy with a hyphema, vitreous hemorrhage, and hypotony. Images in the temporal and nasal meridians revealed thickened tissue bands extending from the peripheral retina to the ciliary body, and from the pars plicata to the posterior surface of the iris. A ciliary body epithelium detachment was seen in the nasal meridian. Ultrasound biomicroscopy demonstrated to be a potential tool in the diagnosis and surgical management of AHFVP.

Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma.

PURPOSE: Although malignant uveal melanoma disseminates predominantly hematogenously because of the absence of intraocular lymphatics, consensus about prognostic impact of microvascular density (MVD) has not been reached. This study was undertaken to investigate whether MVD, microvascular patterns, or both determine prognosis of uveal melanoma. METHODS: A population-based retrospective cohort study of melanoma-specific and all-cause mortality of 167 consecutive patients who had an eye enucleated because of choroidal or ciliary body melanoma from 1972 through 1981 was conducted. MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epitope, factor VIII-related antigen (FVIII-RAg), and alpha-smooth muscle actin (SMA). Kaplan-Meier and Cox regression analyses of survival were performed. The association between MVD and tumor size and location, cell type, and microvascular patterns was assessed. RESULTS: MVD could be determined from 134 of 167 melanomas (80%). Based on globally highest count obtained with antibodies to CD34, MVD ranged from 5 to 121 vessels/0.313 mm2 (median, 40) and its association with presence of microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.028), and largest basal tumor diameter (P = 0.0029) was statistically significant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.29, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mortality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg, whereas MVD obtained with antibodies to SMA was not associated with prognosis. Cox regression showed a hazard ratio of 2.45 (95% CI, 1.43-4.18) for presence of epithelioid cells, 1.11 (95% CI, 1.03-1.20) for largest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed MVD, and 1.51 (95% CI, 1.09-2.10) for presence of loops and networks, all of which independently contributed to prognosis. CONCLUSIONS: The findings support the theory that both MVD and microvascular patterns contribute independently to prognosis in uveal melanoma in addition to cell type and size of the tumor.

High-resolution ultrasonic imaging of blood flow in the anterior segment of the eye.

PURPOSE: To develop a noninvasive technique to visualize and measure blood flow in the iris and ciliary body. METHODS: Echo data from 50-MHz ultrasound scans of the iris and ciliary body of rabbits were digitized using a new "swept scan" modality. The method makes use of spatial oversampling to identify regions with scatterers whose range changes with time. The data allowed construction of high-resolution B-mode images with embedded flow information. Pulsatility over the cardiac cycle was evaluated by sending a series of pulses along a single line of sight containing a vessel of interest. Local blood flow and changes over the cardiac cycle before and after application of atropine were quantified. RESULTS: Flow was identified in the radial vessels and major arterial circle of the iris. Vessels with lumens as small as 40 microm in diameter and flow velocities as low as 0.6 mm/sec were measured. Change in blood velocity over the cardiac cycle was determined to be approximately 27%. Peak systolic velocity after administration of topical atropine increased by 72%. CONCLUSIONS: This technique allowed visualization of flow using the same type of very-high-frequency transducer now widely used for imaging the anterior segment. The technique can also be used at lower frequencies for more posterior tissues with similar improvement of resolution over Doppler. The ability to examine flow in the anterior segment of the eye offers a new tool for study of glaucoma, hypotony, tumors, and other disorders.

Distribution of prognostically important vascular patterns across multiple levels in ciliary body and choroidal melanomas.

PURPOSE: To investigate the validity of assigning patients whose eyes have been removed for ciliary body or choroidal melanoma to risk groups for metastasis based on the identification of microcirculatory patterns in one cross-section taken from the center of the tumor. METHODS: Multiple levels were cut through the blocks of 15 ciliary body or choroidal melanomas until the tumor was exhausted. Each level was examined for the presence of microvascular networks and parallel vessels with cross-linking histologic features strongly associated with death from metastatic melanoma. RESULTS: The central histologic section did not contain either microvascular networks or parallel vessels with cross-linking in eight tumors, nor were these patterns encountered in any of the more peripheral levels of the tumor. Seven tumors contained at least one focus of either microvascular networks or parallel vessels with cross-linking in the central histologic section. In two tumors, at least one of these patterns appeared in all histologic levels; in five tumors, at least one of these patterns appeared through multiple levels until just before the tumor was exhausted from the block (0.24 to 0.85 mm from the edge of the tumor). CONCLUSIONS: This study suggests that the prognostic classification of uveal melanoma based on the histologic profile of the microcirculation may be consistent throughout the tumor depth.