Iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty in refractory glaucoma: case series.

BACKGROUND: Ultrasound cycloplasty is a noninvasive surgery used to reduce intraocular pressure in patients with glaucoma, with fewer severe complications. This report presents several cases of iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty. CASE PRESENTATION: Six patients diagnosed with refractory glaucoma underwent ultrasound cycloplasty at our clinic. Three cases developed iris neovascularization at postoperative day 3, week 2 and week 4 respectively, with intraocular pressure ranging from 12 to 24 mmHg. The other three cases developed neurotrophic keratopathy at postoperative week 3, week 6 and week 8 which completely healed within 60 days. CONCLUSIONS: Iris neovascularization and neurotrophic keratopathy can be triggered after ultrasound cycloplasty, which are uncommon and self-limited but potentially vision-threatening. Preoperative risk assessment and regular postoperative follow-up are recommended to manage complications effectively.

Current clinical applications of anterior segment optical coherence tomography angiography: a review.

Optical coherence tomography (OCT) is a revolutionary in vivo imaging technology that presents real-time information on ocular structures. Angiography based on OCT, known as optical coherence tomography angiography (OCTA), is a noninvasive and time-saving technique originally utilized for visualizing retinal vasculature. As devices and built-in systems have evolved, high-resolution images with depth-resolved analysis have assisted ophthalmologists in accurately localizing pathology and monitoring disease progression. With the aforementioned advantages, application of OCTA has extended from the posterior to anterior segment. This nascent adaptation showed good delineation of the vasculature in the cornea, conjunctiva, sclera, and iris. Thus, neovascularization of the avascular cornea and hyperemia or ischemic changes involving the conjunctiva, sclera, and iris has become prospective applications for AS-OCTA. Although traditional dye-based angiography is regarded as the gold standard in demonstrating vasculature in the anterior segment, AS-OCTA is expected to be a comparable but more patient-friendly alternative. In its initial stage, AS-OCTA has exhibited great potential in pathology diagnosis, therapeutic evaluation, presurgical planning, and prognosis assessments in anterior segment disorders. In this review of AS-OCTA, we aim to summarize scanning protocols, relevant parameters, and clinical applications as well as limitations and future directions. We are sanguine about its wide application in the future with the development of technology and refinement in built-in systems.

Iris aneurysm in feline hypertensive oculopathy.

OBJECTIVE: To describe and document the prevalence and cause of iris aneurysm in feline hypertensive oculopathy. ANIMALS STUDIED: Privately owned cats with systemic hypertension presented for sudden visual deficits and/or hyphema. PROCEDURES: A retrospective search of medical records of cats with systemic hypertension was performed in a specialized eye practice from October 2001 to August 2016. Inclusion criteria used for further evaluation were (1) systolic blood pressure exceeding 170 mm Hg measured by Doppler ultrasound, (2) typical fundus changes consistent with systemic hypertension (retinal folds, retinal edema, intraretinal bullous fluid accumulation, retinal detachment-partial or total, intra-/preretinal bleeding) in at least one eye, and (3) at least one follow-up visit with documented response to therapy with amlodipine. Cats with bilateral hyphema were excluded. RESULTS: A total of 206 cats fulfilled the inclusion criteria. Twenty-eight cats (14%) showed an aneurysm of the iridal vessels, 21 75% with some amount of hyphema. In total, hyphema was present in 62 cats (30%). Pearson correlation of fundus changes, hyphema, and aneurysm was performed. A high correlation between fundus changes without posterior segment hemorrhage and hyphema was found. The histopathology of one eye showed iridial vascular changes compatible with an aneurysm. In 75 cats, additional blood analysis was performed. Presumed chronic kidney disease (80%) was the most common cause of systemic hypertension with eye disease, followed by hyperthyroidism (20%). CONCLUSION: Vascular changes of the iris compatible with aneurysms were seen in 14% of cats with systemic hypertension and may result in vascular rupture and acute hyphema.

Contrast-enhanced ultrasonography for evaluation of blood perfusion in normal canine eyes.

OBJECTIVE: This study was performed to evaluate ocular structures using contrast-enhanced ultrasonography (CEUS) in dogs to assess the feasibility of CEUS for investigating the blood perfusion of canine eyes. ANIMAL STUDIED: Eight purpose-bred beagles were used. PROCEDURES: Blood perfusion and vascularity of the right eye were evaluated using color Doppler, power Doppler, and CEUS with Sonazoid® . Vascular changes were quantitatively evaluated by measuring peak intensity, time to initial upslope, and time to peak from the ciliary body, iris, choroid, retina, and the retrobulbar region by CEUS. RESULTS: On CEUS images, all parts of the examined ocular structures were markedly enhanced and clearly identified from the adjacent region. After injection, the contrast agent initially flowed to the choroid and retina at 14.2 seconds, then to the ciliary body and iris at 20 seconds. The blood signal reached its peak intensity in the ciliary body at 27.2 seconds (47.4 ± 10.63), in the iris at 31.6 seconds (74.00 ± 41.85), and in the retrobulbar region at 23.4 seconds (149 ± 24.59). The optic nerve was clearly distinguished from the retrobulbar region over 5 minutes after the initiation of CEUS. Significantly, more vascular signals were detected in the ciliary body and iris by CEUS than by color and power Doppler. CONCLUSION: Blood perfusion of the intraocular structures and the retrobulbar region can be quantitatively and qualitatively analyzed by CEUS. CEUS may be a useful, noninvasive, and sensitive tool for the evaluation of blood perfusion in ocular diseases.

Comparison of anterior segment optical coherence tomography angiography and fluorescein angiography for iris vasculature analysis.

PURPOSE: The aim of this study is to perform imaging of irises of different colors using spectral domain anterior segment optical coherence tomography angiography (AS-OCTA) and iris fluorescein angiography (IFA) and compare their effectiveness in examining iris vasculature. METHODS: This is a cross-sectional observational clinical study. Patients with no vascular iris alterations and different pigmentation levels were recruited. Participants were imaged using OCTA adapted with an anterior segment lens and IFA with a confocal scanning laser ophthalmoscope (cSLO) adapted with an anterior segment lens. AS-OCTA and IFA images were then compared. Two blinded readers classified iris pigmentation and compared the percentage of visible vessels between OCTA and IFA images. RESULTS: Twenty eyes of 10 patients with different degrees of iris pigmentation were imaged using AS-OCTA and IFA. Significantly more visible iris vessels were observed using OCTA than using FA (W = 5.22; p < 0.001). Iris pigmentation was negatively correlated to the percentage of visible vessels in both imaging methods (OCTA, rho = - 0.73, p < 0.001; IFA, rho = - 0.77, p < 0.001). Unlike FA, AS-OCTA could not detect leakage of dye, delay, or impregnation. Nystagmus and inadequate fixation along with motion artifacts resulted in lower quality images in AS-OCTA than in IFA. CONCLUSIONS: AS-OCTA is a new imaging modality which allows analysis of iris vasculature. In both AS-OCTA and IFA, iris pigmentation caused vasculature imaging blockage, but AS-OCTA provided more detailed iris vasculature images than IFA. Additional studies including different iris pathologies are needed to determine the most optimal scanning parameters in OCTA of the anterior segment.

PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development.

The anterior eye is comprised of an avascular cornea surrounded by a dense periocular vascular network and therefore serves as an excellent model for angiogenesis. Although signaling through PlexinD1 underlies various vascular patterning events during embryonic development, its role during the formation of the periocular vascular network is yet to be determined. Our recent study showed that PlexinD1 mRNA is expressed by periocular angioblasts and blood vessels during ocular vasculogenesis in patterns that suggest its involvement with Sema3 ligands that are concurrently expressed in the anterior eye. In this study, we used in vivo knockdown experiments to determine the role of PlexinD1 during vascular patterning in the anterior eye of the developing avian embryos. Knockdown of PlexinD1 in the anterior eye caused mispatterning of the vascular network in the presumptive iris, which was accompanied by lose of vascular integrity and profuse hemorrhaging in the anterior chamber. We also observed ectopic vascularization of the cornea in PlexinD1 knockdown eyes, which coincided with the formation of the limbal vasculature in controls. Finally we show that Sema3E and Sema3C transcripts are expressed in ocular tissue that is devoid of vasculature. These results indicate that PlexinD1 plays a critical role during vascular patterning in the iris and limbus, and is essential for the establishment of corneal avascularity during development. We conclude that PlexinD1 is involved in vascular response to antiangiogenic Sema3 signaling that guides the formation of the iris and limbal blood vessels by inhibiting VEGF signaling.

Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors.

PURPOSE: To evaluate tumor vasculature with optical coherence tomography angiography (OCTA) in malignant iris melanomas and benign iris lesions. DESIGN: Cross-sectional observational clinical study. PARTICIPANTS: Patients with iris lesions and healthy volunteers. METHODS: Eyes were imaged using OCTA systems operating at 1050- and 840-nm wavelengths. Three-dimensional OCTA scans were acquired. Iris melanoma patients treated with radiation therapy were imaged again after I-125 plaque brachytherapy at 6 and 18 months. MAIN OUTCOME MEASURES: OCT and OCTA images, qualitative evaluation of iris and tumor vasculature, and quantitative vessel density. RESULTS: One eye each of 8 normal volunteers and 9 patients with iris melanomas or benign iris lesions, including freckles, nevi, and an iris pigment epithelial (IPE) cyst, were imaged. The normal iris has radially oriented vessels within the stroma on OCTA. Penetration of flow signal in normal iris depended on iris color, with best penetration seen in light to moderately pigmented irides. Iris melanomas demonstrated tortuous and disorganized intratumoral vasculature. In 2 eyes with nevi there was no increased vascularity; in another, fine vascular loops were noted near an area of ectropion uveae. Iris freckles and the IPE cyst did not have intrinsic vascularity. The vessel density was significantly higher within iris melanomas (34.5%±9.8%, P < 0.05) than in benign iris nevi (8.0%±1.4%) or normal irides (8.0%±1.2%). Tumor regression after radiation therapy for melanomas was associated with decreased vessel density. OCTA at 1050 nm provided better visualization of tumor vasculature and penetration through thicker tumors than at 840 nm. But in very thick tumors and highly pigmented lesions even 1050-nm OCTA could not visualize their full thickness. Interpretable OCTA images were obtained in 82% of participants in whom imaging was attempted. CONCLUSIONS: This is the first demonstration of OCTA in iris tumors. OCTA may provide a dye-free, no-injection, cost-effective method for monitoring a variety of tumors, including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field.

Ultrasound biomicroscopy and tonometry in ophthalmologically normal pigeon eyes.

OBJECTIVE: To evaluate the feasibility of ultrasound biomicroscopy (UBM) and tonometry in pigeons and to provide biometric reference ranges for normal pigeon eyes. ANIMALS STUDIED: Ten pigeons (Columba livia var. domestica) with ophthalmologically normal eyes. PROCEDURES: Ophthalmic examinations, including slit-lamp biomicroscopy and tonometry, were performed to confirm that the eyes were normal. UBM was then performed on the left eye. On each obtained image, the ciliary cleft (CC) length, CC width, and CC area, and iridocorneal angle (ICA) were measured. RESULTS: Richly vascularized iris was observed in all pigeon eyes. Mean intraocular pressure was 11.7 ± 1.6 mmHg, without any statistical difference between the left and right eyes. The UBM scanning procedure was well tolerated in all pigeons. Mean values of CC length, CC width, CC area, and ICA were 1.55 ± 0.17 mm, 0.36 ± 0.05 mm, 0.39 ± 0.04 mm2 , and 15.17 ± 1.06°, respectively. CONCLUSIONS: Ultrasound biomicroscopy could be a useful diagnostic tool to evaluate anterior ocular segment of pigeons.

Microvasculature of the California sea lion (Zalophus californianus) eye and its functional significance.

OBJECTIVE: To examine the ocular circulation in California sea lions (Zalophus californianus). ANIMALS STUDIED: Eyes were obtained postmortem from three sea lions that died while in captivity. PROCEDURES: Specimens from sea lions were investigated using scanning electron microscopy (SEM) of vascular corrosion casts. The thermal characteristics of live animal eyes were measured using an infrared imaging system. RESULTS: The major orbital artery of the sea lion was the ophthalmic artery. The artery was remarkably thick in diameter, showed a marked convolution and formed an ophthalmic rete around the optic nerve at the posterior pole of the eyeball. The long posterior ciliary artery terminates to form a prominent inner arterial circle at the pupillary margin. The iridial arteries originated from the arterial circle showing either a crimped or somewhat coiled course, extending toward the root of the iris and formed a root supplying a large amount of blood to the iris and ciliary bodies. The venules in the conjunctiva formed a well-developed venous plexus. The vortex veins showed a dilation and constriction at the site passing through the sclera. Thermographic examination revealed that the eye showed a higher degree of thermal emission than adjacent skin areas. CONCLUSIONS: These characteristics suggest that the ocular vasculature might play roles in thermoregulation as well as in hemodynamics by draining a large amount of blood so that the appropriate operating temperature for the eye can be maintained in a deep and cold aquatic environment.

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.

Late complications after brachytherapy of I-125 uveal melanoma. / Ocena odleglych powiklan po brachyterapii I-125 czerniaka blony naczyniowej.

Purpose: To assess the late complications after the I-125 brachytherapy of uveal melanoma. Material and methods: 129 patients (71 women ­ 55%, and 58 men ­ 45%) treated at the Department of Ophthalmology and Ocular Oncology of the University Hospital in Krakow between January 2005 and December 2009 were evaluated. I-125 isotope applicators were used for tumor irradiation. The mean follow-up was 42.5 months. Results: The following complications were observed: radiation cataract, secondary glaucoma, radiation retinopathy, radiation maculopathy, necrosis of sclera, retinal and vitreous hemorrhages and retinal detachment. Post-radiation cataract was the most common late complication (90.5­94.7%). Conclusions: Despite the undoubted effectiveness in the treatment of uveal melanomas, I-125 brachytherapy poses a high risk of complications. Tumor location in the proximity of critical visual structures negatively affected ultimate visual function. The tumor size and the dose of irradiation significantly affected the incidence of radiation-induced complications.

Quantitative study of the microvasculature and its endothelial cells in the porcine iris.

The roles of the iris microvasculature have been increasingly recognised in the pathogenesis of glaucoma and cataract; however limited information exists regarding the iris microvasculature and its endothelium. This study quantitatively assessed the iris microvascular network and its endothelium using intra-luminal micro-perfusion, fixation, and staining of the porcine iris. The temporal long posterior ciliary artery of 11 isolated porcine eyes was cannulated, perfusion-fixed and labelled using silver nitrate. The iris microvasculature was studied for its distribution, orders and endothelial morphometrics. The density of three layers of microvasculature was measured. Endothelial cell length and width were measured for each vessel order. The iris has an unusual vascular distribution which consisted of abundant large vessels in the middle of the iris stroma, branching over a relatively short distance to the microvasculature located in the superficial and deep stroma as well as the pupil edge. The average vascular density of the middle, superficial, and deep layers were 38.9 ± 1.93%, 10.9 ± 1.61% and 8.0 ± 0.79% respectively. Multiple orders of iris vessels (capillary, 6 orders of arteries, and 4 orders of veins) with relatively large capillary and input arteries (319.5 ± 25.6 µm) were found. Significant heterogeneity of vascular diameter and shape of the endothelia was revealed in different orders of the iris vasculature. Detailed information of topography and endothelium of the iris microvasculature combined with unique structural features of the iris may help us to further understand the physiological and pathogenic roles of the iris in relevant ocular diseases.

Intracellular cytoskeleton and junction proteins of endothelial cells in the porcine iris microvasculature.

Recently we reported studies of the iris microvasculature and its endothelial cells using intra-luminal micro-perfusion, fixation, and silver staining, suggesting that the iris vascular endothelium may be crucial for maintaining homeostasis in the ocular anterior segment. Here we present information regarding the intracellular structure and cell junctions of the iris endothelium. Thirty-seven porcine eyes were used for this study. The temporal long posterior ciliary artery was cannulated to assess the iris microvascular network and its endothelium using intra-luminal micro-perfusion, fixation, and staining with phalloidin for intracellular cytoskeleton f-actin, and with antibodies against claudin-5 and VE-cadherin for junction proteins. Nuclei were counterstained with Hoechst. The iris was flat-mounted for confocal imaging. The iris microvasculature was studied for its distribution, branch orders and endothelial morphometrics with endothelial cell length measured for each vessel order. Our results showed that morphometrics of the iris microvasculature was comparable with our previous silver staining. Abundant stress fibres and peripheral border staining were seen within the endothelial cells in larger arteries. An obvious decrease in cytoplasmic stress fibres was evident further downstream in the smaller arterioles, and they tended to be absent from capillaries and veins. Endothelial intercellular junctions throughout the iris vasculature were VE-cadherin and claudin-5 immuno-positive, indicating the presence of both adherent junctions and tight junctions between vascular endothelial cells throughout the iris microvasculature. Unevenness of claudin-5 staining was noted along the endothelial cell borders in almost every order of vessels, especially in veins and small arterioles. Our results suggest that significant heterogeneity of intracellular structure and junction proteins is present in different orders of the iris vasculature in addition to vascular diameter and shape of the endothelia. Detailed information of the topography and intracellular structure and junction proteins of the endothelium of the iris microvasculature combined with unique structural features of the iris may help us to further understand the physiological and pathogenic roles of the iris vasculature in relevant ocular diseases.

Distribution of galanin receptors in the human eye.

The neuropeptide galanin (GAL) is widely distributed within intrinsic and extrinsic sources supplying the eye. It is involved in regulation of the vascular tone, thus important for ocular homeostasis. Since the presence/distribution of its receptors is unknown, we here screen for the presence of the various GAL receptors in the human eye. Meeting the Helsinki-Declaration, human eyes (n = 6; 45-83 years of age, of both sex, post mortem time 10-19 h) were obtained from the cornea bank and prepared for immunohistochemistry against GAL receptors 1-3 (GALR1-GALR3). Over-expressing cell assays served as positive controls and confocal laser-scanning microscopy was used for documentation. Cell assays reliably detected immunoreactivity for GALR1-3 and cross-reactions between antibodies used were not observed. In the cornea, GALR1-3 were detected in basal layers of the epithelium, stroma, endothelium, as well as in adjacent conjunctiva. In the iris, GALR1-3 were detected in iris sphincter and dilator, while iris vessels displayed immunoreactivity for GALR1 and GALR3. In the ciliary body, GALR1 was exclusively found in the non-pigmented epithelium while GALR3 was detected in the ciliary muscle and vessels. In the retina, GALR1 was present in fibers of the IPL, OPL, NFL, many cells of the INL and few cells of the ONL. GALR2 and GALR3 were present in few neurons of the INL, while GALR2 was also found surrounding retinal vessels. RPE displayed weak immunoreactivity for GALR2 but intense immunoreactivity for GALR3. In the choroid, GALR1-3 were detectable in intrinsic choroidal neurons and nerve fibers of the choroidal stroma, and all three receptors were detected surrounding choroidal blood vessels, while the choriocapillaris was immunoreactive for GALR3 only. This is the first report of the various GALRs in the human eye. While the presence of GALRs in cornea and conjunctiva might be relevant for wound healing or inflammatory processes, the detection in iris vessels (GALR1, 2) and choroidal vessels (GALR1-3) highlights the role of GAL in vessel dynamics. Presence of GALR1 in ciliary body epithelium and GALR3 in ciliary vessels indicates involvement in aqueous humor production, whereas retinal GALR distribution might contribute to signal transduction.

Inducible and endothelial nitric synthetase expression and nitrotyrosine accumulation in iris vasculature of patients with primary open-angle glaucoma: a pilot study.

BACKGROUND: The "double-faced" effect of nitric oxide (NO) is thought to play an important role in triggering and progression of glaucoma. MATERIAL/METHODS: Iris samples were obtained during iridectomy in 35 patients (mean age of 65.4±5.3 years) with diagnosed primary open-angle glaucoma (POAG). The controls were collected postmortem from 10 donors with a mean age of 62.2±1.9 years. Visual field defects were evaluated by perimetry. The Hodapp-Parrish-Anderson classification was used to divide patients into 3 visual field defect groups. The intraocular pressure was measured 3 times before surgery using applanation tonometry. The phenotype activity of nitric oxide synthase (NOS) isoenzymes (endothelial--eNOS and inducible--iNOS) and expression of nitrotyrosine in iris vasculature was assessed. RESULTS: Significant differences were found between glaucoma patients and the controls in eNOS and iNOS activity (Mann-Whitney test, U=35.5, Z=-2.037, p=0.04 and U=21, Z=2.69, p=0.007, respectively). In addition, the results showed an upregulation of nitrotyrosine in the capillary endothelial cells in the study group, which was associated with the duration of diagnosed glaucoma (R-Spearman of 0.33, p=0.0047) and visual field mean defect MD (R-Spearman of 0.29, p=0.019). Moreover, the activity of nitrotyrosine was significantly correlated with iNOS immunoreactivity (R-Spearman of 0.5, p=0.0001). However, the iNOS activity significantly varied among Hodapp-Parrish-Anderson groups (p=0.03). CONCLUSIONS: Our observations confirmed the association between glaucomatous disturbances and upregulation of iNOS, together with increased nitrotyrosine storage.

[Effect of Intravitreal Bevacizumab Injection on Iris and Iridocorneal Angle Neovascularization in Neovascular Glaucoma].

Neovascular glaucoma is a serious complication associated with retinal ischemic changes, which increase the production of vascular endothelial growth factor. Vascular endothelial growth factor has been implicated as a key molecule in the development of newly formed vessels and neovascular glaucoma. Intravitreal injection of bevacizumab, a full-length humanized anti-vascular endothelial growth factor monoclonal antibody, leads to a dramatic regression of the new iris and iridocorneal angle vessels on slitlamp examination. However, anterior segment angiography reveals that bevacizumab does not cause a regression of the neovascular vessels themselves but reduces vascular permeability while newly formed vessels are still present in the iris and iridocorneal angle. This review focuses on the pathology and diagnosis of neovascula glaucoma and the effect of intravitreal bevacizumab on the iris and iridocorneal angle neovascularization.

The effect of central retinal venous pressure in patients with central retinal vein occlusion and a high mean area of nonperfusion.

PURPOSE: To evaluate the effect of central venous pressure (CVP) on visual outcomes and retinal ischemic consequences in patients with central retinal vein occlusion (CRVO). DESIGN: Prospective, single-center cohort study. PARTICIPANTS: Eighty-eight patients with CRVO and a high overall mean area (21.6 disc areas) of capillary nonperfusion (CNP) who were followed for 18 months before the availability of intravitreal therapy and who were offered standard care of the time. METHODS: Patients were evaluated at baseline and at 3, 8, and 18 months. At each study visit, measurements of CVP, best-corrected visual acuity (BCVA), area of CNP, retinal fluorescein transit time (FTT), and an evaluation for rubeosis iridis were performed. MAIN OUTCOME MEASURES: Evaluation of the effect of different levels of CVP on BCVA, retinal blood flow, and the development of retinal ischemia and rubeosis iridis. RESULTS: Mean BCVA was significantly higher in patients with lower CVP at all time points (P<0.0001). The area of CNP increased significantly with higher levels of CVP and progressed with time. The development of rubeosis iridis was significantly associated with CVP at all time points and was present in 5.6%, 27.9%, and 88.9% of those with low, moderate, and high CVP levels, respectively (P<0.0001), at the 18-month conclusion. Retinal blood flow as measured by FTT was reduced with higher levels of CVP. Spontaneous lowering of CVP had beneficial effects on BCVA, although this diminished with time. CONCLUSIONS: Eyes with increased CVP after more severe CRVO demonstrate significantly reduced vision, reduced retinal blood flow, a higher incidence of rubeosis iridis, and larger areas of CNP that correlate with the degree of CVP elevation.

In vivo OCT microangiography of rodent iris.

We report on the functional optical coherence tomography (OCT) imaging of iris tissue morphology and microcirculation in living small animals. Anterior segments of healthy mouse and rat eyes are imaged with high-speed spectral domain OCT (SD-OCT) utilizing ultrahigh sensitive optical microangiography (UHS-OMAG) imaging protocol. 3D iris microvasculature is produced by the use of an algorithm that calculates absolute differences between the amplitudes of the OCT interframes. We demonstrate that the UHS-OMAG is capable of delineating iris microvascular beds in the mouse and rat with capillary-level resolution. Furthermore, the fast imaging speed enables dynamic imaging of iris micro-vascular response during drug-induced pupil dilation. We believe that this OCT angiographic approach has a great potential for in situ and in vivo monitoring of the microcirculation within iris tissue beds in rodent disease models that have microvascular involvement.

von Willebrand factor in iris vasculature of glaucoma patients.

BACKGROUND: Previous reports have indicated the role of endothelium disturbances, as expressed by von Willebrand factor (vWF) release, in pathophysiology of glaucoma. The objective of this study was to investigate the vWF expression in iris vasculature of patients with primary open-angle glaucoma (POAG). MATERIAL AND METHODS: Immunohistochemistry of vWF expression was performed on cryostat sections of samples collected at the time of peripheral iridectomy and controls collected from dead donors. RESULTS: Twenty-seven Caucasians age 66.6±3.7 with 5.8±3.7-year history of treated PAOG and 10 controls age 62.2±1.92 with no history of glaucoma. The percentage of patients who presented normal and up-regulation of vWF phenotype expression differed statistically between examined and control groups: 48% versus 100% (p=0.035, chi-square test with Yates' correction). Sex, age, glaucoma duration, and visual field quantitative indices had no impact on vWF expression. A significant correlation between mean pre-surgery intraocular pressure and vWF expression was found (Spearman r=0.42, p=0.03). CONCLUSIONS: Considering the results, it may be suggested that vWF is actively involved in the pathophysiology of glaucoma.

The influence of new beta-adrenolytics nebivolol and carvedilol on intraocular pressure and iris blood flow in rabbits.

BACKGROUND: The aim of this study was to assess the influence of propranolol, nebivolol, and carvedilol on intraocular pressure and blood flow in vessels of rabbit's (New Zealand White) eyeball. METHODS: The study was carried out on New Zealand white rabbits. Intraocular pressure was measured with the applanation tonometer Möller-Wedel and Icare; blood flow was measured with Doppler Laser Blood Flow Monitor MBD3. RESULTS: Following a single administration into a conjunctival sac, all drugs decreased intraocular pressure. Iris blood flow was decreased following administration of propranol, but increased by nebivolol and carvedilol. After single and repeated oral administration of nebivolol and carvedilol an IOP decrease was demonstrated, but with no effect of all applied doses on iris or retina/choroid blood flow. CONCLUSION: Studies performed on an animal model indicate that it is possible to reduce the intraocular pressure and increase ocular blood flow in humans, following topical administration of carvedilol and nebivolol. Confirmation of those results in clinical trials may lead to development of a new anti-glaucoma treatment. Further clinical studies of long-term nebivolol and carvedilol are recommended. They are necessary for evaluation of usefulness of those drugs for selected groups of patients, for example those with glaucoma and arterial hypertension.