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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., (© 2024. The Author(s).)

Introduction: Anterior segment ischemia (ASI) is a rare but potentially sight-threatening complication of strabismus surgery. Preoperative imaging of the iris vasculature may be appropriate in patients at high risk of ASI. In clinical practice, this is currently done through invasive fluoresceine or indocyanine green (ICG) angiography and in study context through laser speckle contrast imaging. The purpose of this study is to investigate the use of noninvasive optical coherence tomography angiography (OCTA) as a screening tool for ASI in strabismus surgery., Methods: A prospective interventional trial was conducted from September until November 2021 at the Leuven University Hospitals. Patients scheduled for strabismus surgery to one or more rectus muscles underwent OCTA preoperatively and at day two postoperatively. The vascular density was calculated for all images with sufficient quality. Information on risk factors for ASI was collected. A two-sided t-test was used for pairwise comparison pre- and postoperatively. Filling defects were qualitatively assessed., Results: Eighteen patients were included. In only seven muscles of five patients, images of sufficient quality on both image acquisition moments were suitable for statistical analysis. The mean age of these patients was 45.2 years and 40% were women. A mean vascular density of 53,099% preoperatively and a mean density of 50,782% postoperatively with a mean decrease of 2.316% ( p  = .318, 95% confidence interval [-2.886; 7.516]) was found. No filling defects were identified., Discussion: The small final number of images contributing to statistical analysis shows that current application of the OCTA technique is hampered by poor image quality and poor repeatability. We identified difficulties in the image acquisition process and variable pupil size due to iris muscle contractions as the two main reasons. We believe that adjustments in the OCTA software such as pupil tracking and tracking of iris vasculature can largely overcome these limitations. Furthermore, there is a need for a normative database to allow good quantitative comparison and risk stratification. We conclude that OCTA could be suitable for screening in prevention of ASI with both qualitative and quantitative analysis if adjustments are made.

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the blood flow and vascular visibility of irises in relation to pigmentation and pupil size, using an anterior segment optical coherence tomography angiography (OCTA)., Materials and Methods: This is a cross-sectional study. OCTA images were acquired in the nasal and temporal quadrants from a cohort of 30 healthy subjects in photopic (miosis) and scotopic (mydriasis) conditions. Patients were divided according to iris color (less pigmented: group L vs more pigmented: group D). Vascular parameters (vessel density (VD), vessel length density (VLD), fractal dimension (FD)) were applied and compared among groups L and D, location and different pupil status. A novel vascular index called Luminance Index (LI) was developed and applied in order to quantify vascular flow and evaluate its variation in photopic and scotopic conditions. Multivariable analyses were performed to evaluate possible predictors of VD and LI., Results: No differences were found for all vascular measurements (VD, VDL, FD, LI) between nasal and temporal quadrants. All vascular measurements were higher in group L than in group D ( p  < 0.05), except for LI and FD in photopic condition. In group L, all vascular parameters increased ( p  < 0.001) after dark adaptation. In group D, only LI increased after dark adaptation ( p  < 0.001). Pigmentation and iris thickness were significantly associated with VD in scotopic and photopic conditions, and with LI only in scotopic condition., Conclusions: Pigmentation still remains a major issue for vascular visibility. Quantitative and qualitative vascular changes follow pupil size variation. LI could be a new surrogate to quantify blood flow.

Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3 -/- and Flt3l -/- mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3 -/- mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3 -/- mice. In Flt3l -/- mice, each DC subsets was severely reduced after laser injury. Neither Flt3 -/- or Flt3l -/- mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD., (© 2021. The Author(s).)

Purpose: To compare anterior segment optical coherence tomography angiography (AS-OCTA) systems in delineating normal iris vessels and iris neovascularisation (NVI) in eyes with pigmented irides., Methods: Prospective study from January 2019 to June 2019 of 10 consecutive patients with normal pigmented iris, had AS-OCTA scans with a described illumination technique, before using the same protocol in five eyes with NVI (clinical stages 1-3). All scans were sequentially performed using a spectral-domain OCTA (SD-OCTA), and a swept-source OCTA (SS-OCTA, Plex Elite 9000). Images were graded by two masked observers for visibility, artefacts and NVI characteristics. The main outcome measure was iris vessel density measurements comparing SS-OCTA and SD-OCTA systems., Results: The median age of subjects was 28 (20-35) years, and 50% were female. The paired mean difference of iris vessel density measurements was 11.7 (95% CI 14.7 to 8.1; p=0.002), SS-OCTA detecting more vessels than SD-OCTA. The inter-rater reliability for artefact score (κ=0.799, p<0.001) and visibility score (κ=0.722; p<0.001) were substantial. Both AS-OCTA systems were able to detect NVI vessels with a fair agreement (κ=0.588), with clearer NVI characteristics in stage 1/2 compared to stage 3 NVI (mean difference NVI score: 2.7±0.4, p=0.009)., Conclusion: The SS-OCTA was better able to delineate iris vessels in normal pigmented irides compared to SD-OCTA. Both AS-OCTA systems identified NVI characteristics based on its atypical configuration or location, but further improvements are needed to allow for more accurate objective, serial quantification for clinical use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose : To characterize the aqueous levels of inflammation and ischemia-related biomarkers in a spectrum of retinal ischemic conditions, including neovascular glaucoma (NVG) with stable iris neovascularization after pan retinal photocoagulation (PRP) and anti-VEGF treatment. Methods : Aqueous samples were collected from 139 eyes including NVG (n = 12), stable NVG (n = 26), CRVO (n = 11), NPDR (n = 18), PACG (n = 18), PDR (n = 25), BRVO (n = 7) and cataract (n = 22). The levels of VEGF-A, IL-8 and EPO were measured with ELISA. Results : Aqueous VEGF-A significantly decreased after anti-VEGF and PRP, from 983.79 ± 821.16 pg/ml in the NVG group (n = 11) to 256.50 ± 51.14 pg/ml in the stable NVG group (n = 24) ( P = .015). Aqueous VEGF-A in stable NVG group (256.50 ± 51.14 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in CRVO (212.10 ± 19.84 pg/ml, n = 7, P = .017), NPDR (221.18 ± 38.21 pg/ml, n = 14, P = .015), BRVO (213.14 ± 48.50 pg/ml, n = 6, P = .028) and cataract group (185.30 ± 34.35 pg/ml, n = 22, P < .001). Aqueous IL-8 in stable NVG group (74.82 ± 10.78 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in CRVO (65.19 ± 15.34 pg/ml, n = 11, P = .032) and cataract group (54.11 ± 12.28 pg/ml, n = 22, P < .001). Aqueous EPO in stable NVG group (17.48 ± 3.02 pg/ml, n = 24) was significantly higher (ANOVA, P < .001) than in BRVO (14.98 ± 2.57 pg/ml, n = 7, P = .034) and cataract group (13.50 ± 2.65 pg/ml, n = 22, P < .001). Aqueous concentrations of VEGF-A and IL-8 correlated positively with IOP (r = 0.413, P < .001, r = 0.349, P < .001, respectively, r = correlation coefficient). VEGF-A correlated positively with IL-8 and EPO ( P < .001, P = .002, respectively). IL-8 correlated positively with EPO ( P < .001). Conclusions : The aqueous levels of VEGF-A, IL-8 and EPO in NVG patients with stable iris neovascularization, who had received PRP and anti-VEGF, were still significantly higher than in control groups with some retinal ischemic conditions.

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., (© 2020 American College of Veterinary Ophthalmologists.)

Aim: To investigate the efficacy and safety of intravitreal Conbercept (IVC) and trabeculectomy for treating neovascular glaucoma (NVG)., Methods: We retrospectively reviewed a total of 29 eyes from 29 NVG patients. All patients received preoperative IVC combined with mitomycin C (MMC) augmented trabeculectomy with a 12-month follow-up. The best-corrected visual acuities (BCVA), intraocular pressure (IOP), and cumulative survival rate were calculated., Results: All 29 cases had complete regression of iris neovascularization at 7 days after the combination treatment, and 2 cases had residual iris neovascularization which regressed completely 1 month later. IOP decreased while BCVA improved significantly following the combination treatment. The success rates were 96.6%, 93.1%, 89.7%, 86.2%, and 82.8% at 1 week, 1, 3, 6, and 12 months after trabeculectomy, respectively. IVC injection combined trabeculectomy had few complications., Conclusions: IVC injection of conbercept combined with trabeculectomy is effective and safe for the treatment of NVG.

A 71-year-old woman presented with spontaneous microhyphema in her left eye, causing blurry vision. Bleeding stopped spontaneously shortly after several cycles of digital compression on the upper eyelid, (which were documented in video), and therefore, did not require laser photocoagulation, a possible approach previously explained to the patient. A microhemangioma at the edge of the iris was identified to be the cause of the condition. The hemorrhage did not recur during the follow-up period (9 months)., Competing Interests: None

Competing Interests: There are no conflicts of interest.

Purpose: To evaluate the effects of clinical features associated with enucleation in eyes with Coats disease., Methods: The medical records of all patients with Coats disease at the Ocular Oncology, Wills Eye Hospital from November 1, 1973, to July 31, 2018, were reviewed retrospectively. The clinical features pertaining to need for ultimate enucleation and time to enucleation were compared., Results: The records of 351 eyes were reviewed, of which 259 had follow-up at our center and 32 (12%) were managed with enucleation. Reasons for enucleation included neovascular glaucoma (n = 24 [75%]), possible tumor (6 [19%]), and phthisis bulbi (2 [6%]). Compared to nonenucleated eyes, enucleated eyes had more extensive clock hour involvement of telangiectasia (P < 0.001), light bulb aneurysms (P < 0.001), exudation (P < 0.001), and subretinal fluid (P < 0.001). On adjusted analysis by binomial logistic regression, variables predictive of enucleation included presence of iris neovascularization (P = 0.01), ultrasonographic retinal detachment (P = 0.004), open-funnel retinal detachment (P = 0.04), closed-funnel retinal detachment (P = 0.01), ultrasonographic elevation of subretinal fluid by millimeters (P = 0.001), and angiographic extent of light bulb aneurysms by clock hours (P = 0.02). By Kaplan-Meier analysis of 4-year cumulative risk of enucleation, risk factors for enucleation included presence of iris neovascularization (hazard ratio [HR] 31.0; P < 0.001), ultrasonographic retinal detachment (HR 56.2; P < 0.001), open-funnel retinal detachment (HR 2.7; P = 0.01), and closed-funnel retinal detachment (HR 4.5; P < 0.001)., Conclusions: Clinical features that predict risk of and time to enucleation in eyes with Coats disease include iris neovascularization, ultrasonographic presence and millimeter-elevation of retinal detachment, and angiographic extent of light bulb aneurysms., (Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

We evaluated regression of iris neovascularization (INV) using en-face anterior-segment optical coherence tomography angiography (AS-OCTA) after anti-vascular endothelial growth factor (VEGF) therapy. Seven consecutive eyes with INV were examined before and after anti-VEGF therapy, and all AS-OCTA scans were obtained using a swept-source OCTA system with an anterior-segment lens adapter. Slit-lamp microscopy photography and anterior indocyanine green angiography also were performed. Quantitative analyses of the vascular density, vascular lacunarity, and fractal dimension on AS-OCTA images were performed. AS-OCTA visualized the INV as signals around the pupillary margin, which corresponded to the vasculature confirmed by slit-lamp microscopy. After anti-VEGF drug injection, regression of INV was observed by AS-OCTA in all eyes (100%). The vascular density decreased and vascular lacunarity increased significantly after anti-VEGF therapy. This pilot study demonstrated the ability of AS-OCTA not only to detect but also to evaluate INV. Further study is warranted to improve the algorithm for delineating the iris vasculature to decrease artifacts.

Purpose: To detect early growth of blood and lymphatic vessels in the mouse cornea and iris after penetrating keratoplasty., Methods: Penetrating keratoplasty was performed with C57BL/6 mice as donors and BALB/c mice as recipients. Graft transparency and neovascularization were examined by slit-lamp microscopy. Whole mounts of the cornea and iris were processed for detection of the outgrowth of blood and lymph vessels., Results: On day 3 after surgery, all corneal grafts were slightly edematous, and blood vessels in the corneoscleral limbus dilated. LYVE-1 lymphatic vessels and CD31 blood vessels were distributed in the peripheral cornea. In the iris, the density of blood vessels increased, and LYVE-1 cells nearly vanished. On day 7, the grafts became opaque, and blood vessels grew into the recipient bed. A great quantity of lymph vessels invaded the cornea. LYVE-1 arborescent cells were found around the lymphatic vessels. In the iris, blood vessels became bulky and stiff, and arborescent LYVE-1 cells increased in number. On day 14, corneal neovascular regression and graft clarity were found. Lymphatic vessels regressed more slowly than blood vessels in the cornea. In the iris, blood vessels remained coarse. Increasing arborescent LYVE-1 cells were also noted in the ciliary body., Conclusions: Our findings suggest that the iris-ciliary body could amplify immune signals and in part promote initiation of immune rejection after keratoplasty by providing a pathway for macrophages, which might participate in corneal lymphangiogenesis.

Introduction: The iris vascular supply originates in the anterior and long posterior ciliary arteries. The endothelium influences local blood flow by releasing endothelium relaxing and contracting substances. From a functional perspective, the ocular vascular tonus adjustment is humoral and neural dependent. Objectives: The present article aims to evaluate the possible implications of topical administration of selective COX2 and nonselective COX inhibitors generically named nonsteroidal anti-inflammatory drugs (NSAIDs) and their possible interactions with the endocannabinoid system and the way they could interfere with the vascular tone at the level of ocular iris territory in Wistar rats. Materials and methods: Experimental protocol on Wistar rats was performed in accordance with present laws regarding animal welfare and ethics in animal experiments (Directive 86/ 609EEC/ 1986; Romanian Law 205/ 2004; Romanian Laws 206/ 2004, 471/ 2002 and 9/ 2008; Romanian Order 143/ 400). The studied substances were instilled topically under general anesthesia, and images of the rat iris vessels were captured over a period of 10 minutes. The obtained images were further analyzed using an appropriate hardware and software program. Results: The nonselective NSAIDs induced vascular dilation in the iris vessels, while the selective COX2 inhibitors determined a variable degree of vasoconstriction. Conclusion: In view of the results of this experiment and the added evidence found in literature, we consider that further research will show the potential benefits for the additional use of NSAIDs in ocular pathology, otherwise unaffected by this medication until the present time (for example, glaucoma treatment).

Purpose: The purpose of this study is to describe the clinical characteristics, multimodality imaging findings, and clinical course of iris varices., Methods: Retrospective, noncomparative, observational case series of 28 eyes of 26 patients with iris varices, diagnosed between 2007 and 2017, has been used., Results: The mean (±SD) age was 58.3 ± 12.5 years (median 57.5, range 37-81). Patients were 57.7% male and 27% hypertensive. Varices were bilateral in two patients. The mean and median visual acuities were both 20/20 (range 20/16-20/40). Intraocular pressures were 16 mmHg (10-23 mmHg). Secondary glaucoma did not occur. The inferotemporal iris quadrant was affected in 75%. A single varix was seen in 64% and 36% appeared multiple. Varix orientation was radial in 57% and circumferential in 21%. Combined radial and circumferential varix orientation was noted in 18%. One had independent radial and circumferential varices in separate quadrants. A single episcleral sentinel blood vessel directed to the varix was present in 36%. Ultrasound biomicroscopy (UBM) showed a slightly increased mean iris thickness of 0.8 mm and multiple echolucent iris stromal vascular channels. Iris angiography showed no leakage of dye. Managed by observation over a mean follow-up of 37.7 months (range, 3-129), 96.4% eyes were stable and one (3.6%) regressed. No corectopia, ectropion uveae, hyphema, or metachronous anterior segment benign or malignant tumors occurred., Conclusion: Iris varix is primarily located in the inferotemporal quadrant and not associated with dysmorphic pupillary findings, progression, secondary glaucoma, or malignancy. Iris varices were benign vasculopathies with no associated ocular or vision-related morbidity., Competing Interests: None

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., (© 2018 American College of Veterinary Ophthalmologists.)

Purpose: To describe the clinical and imaging findings and treatment options in a series of patients with iris microhemangiomatosis., Design: Retrospective observational case series., Methods: Setting: Single institution., Study Population: Twenty-two eyes of 14 consecutive patients with iris microhemangiomatosis were reviewed., Observation Procedures: Clinical examination and slit-lamp photography were performed on every patient. Anterior segment optical coherence tomography (AS-OCT), anterior segment optical coherence tomography angiography (AS-OCTA), anterior segment intravenous fluorescein angiography (AS-IVFA), and ultrasound biomicroscopy were performed when possible., Main Outcome Measures: Clinical and imaging features and treatment strategies., Results: Twenty-two eyes of 14 patients with iris microhemangiomatosis were included in this series. Mean patient age was 70 years (range, 58-82 years), and all patients were white. The iris hemangiomatosis appeared as subtle, multifocal, ectatic vascular channels arranged circumferentially at the pupillary margin. Iris color was blue (n = 19 eyes) or green (n = 3 eyes), and the features were unilateral (n = 6 patients) or bilateral (n = 8 patients). Additional features included reduced visual acuity (n = 13 eyes), hyphema (n = 12 eyes), and glaucoma (n = 7 eyes). There was no history of ocular trauma or systemic vasculopathic conditions. AS-OCT documented the fine tuft at the pupillary margin, AS-OCTA showed vascular flow, and AS-IVFA demonstrated pupillary margin vascular lesions with mild staining. Observation was advised in 20 cases (91%), and argon laser photocoagulation was required for repetitive hyphema in 2 cases (9%)., Conclusion: Iris microhemangiomatosis is a rare ocular condition, often manifesting with spontaneous unilateral hyphema and/or secondary glaucoma. AS-IVFA confirms the diagnosis, and intervention with laser photocoagulation is necessary in only 9% of eyes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Anterior segment ischemia (ASI) is a rare but potentially serious complication of strabismus surgery. Indocyanine green angiography and fluorescein angiography have been used to reveal iris-filling defects for clinicians considering a patient's risk of ASI. However, both are limited by invasive and time-consuming nature and potential adverse effects. Recently, optic coherence tomography angiography (OCT-A) has been introduced and used to image iris vasculature in individuals without abnormalities., Objective: To determine the use of iris OCT-A for patients undergoing strabismus surgery and who are at risk for ASI., Design, Setting, and Participants: This prospective case series study took place in an academic center. Adults undergoing strabismus surgery on at least 1 vertical muscle were prospectively recruited. The study took place from June to November 2017, and analysis began in January 2018., Interventions: Indocyanine green angiography and OCT-A of the iris preoperatively and 1 day postoperatively., Main Outcomes and Measures: A masked examiner evaluated all images and determined whether any filling defects were present qualitatively (lack of perfusion) and quantitatively (for OCT-A using internal software to calculate vessel density)., Results: Ten eyes of 9 individuals (mean [SD] age, 63 [11] years) were included. Two individuals (22.2%) identified as Hispanic, and 7 (77.8%) identified as white. There were 6 women (66.7%). The mean preoperative vessel density (percentage of the area occupied by vessels) averaged for all quadrants decreased from 57% preoperatively to 55% postoperatively (mean difference, 2%; 95% CI, 0.4%-4.2%; P = .05). When comparing quadrants adjacent to operated muscles, the mean vessel density decreased from 56% to 53% (mean difference, 2.6%; 95% CI, 0.17%-4.8%; P = .02). In addition, OCT-A detected vascular filling defects in the quadrant adjacent to the operated muscle on the patients in whom they were present (n = 1, inferior rectus recession)., Conclusions and Relevance: In this preliminary study, OCT-A determined iris vessel filling defects when present. In addition, OCT-A gives qualitative vessel density values that can be compared preoperatively and postoperatively although the clinical relevance of small differences is not known. While only 10 eyes were evaluated, and as such generalizability of these findings cannot be determined, the results suggest that OCT-A may be a useful tool in the evaluation of patients undergoing strabismus surgery to determine whether a patient is at risk to develop ASI.

For the diagnosis and evaluation of ophthalmic diseases, imaging and quantitative characterization of vasculature in the iris are very important. The recently developed photoacoustic imaging, which is ultrasensitive in imaging endogenous hemoglobin molecules, provides a highly efficient label-free method for imaging blood vasculature in the iris. However, the development of advanced vascular quantification algorithms is still needed to enable accurate characterization of the underlying vasculature. We have developed a vascular information quantification algorithm by adopting a three-dimensional (3-D) Hessian matrix and applied for processing iris vasculature images obtained with a custom-built optical-resolution photoacoustic imaging system (OR-PAM). For the first time, we demonstrate in vivo 3-D vascular structures of a rat iris with a the label-free imaging method and also accurately extract quantitative vascular information, such as vessel diameter, vascular density, and vascular tortuosity. Our results indicate that the developed algorithm is capable of quantifying the vasculature in the 3-D photoacoustic images of the iris in-vivo, thus enhancing the diagnostic capability of the OR-PAM system for vascular-related ophthalmic diseases in vivo., ((2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

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.

We describe a model of puncture-induced iris neovascularization as a general model for noninvasive evaluation of angiogenesis. The model is also relevant for targeting neovascular glaucoma, a sight-threatening complication of diabetic retinopathy. This method is based on the induction of iris vascular response by a series of self-sealing uveal punctures on BALB/c mice and takes advantage of the postpartum maturation of mouse ocular vasculature. Mouse pups undergo uveal punctures from postnatal day 12.5, when the pups naturally open their eyes, until postnatal day 24.5. Due to the transparency of the cornea, iris vasculature can be analyzed easily through time by noninvasive in vivo methods. Furthermore, the semitransparent iris of BALB/c mice can be flatmounted for detailed immunohistologic analysis with minimal non-specific background staining. In this model, angiogenesis is mainly driven by the inflammatory and plasminogen activating systems. The puncture-induced model is the first to induce iris neovascularization in small rodents, and has the advantage of allowing direct noninvasive in vivo analysis of the angiogenic process. Moreover, the model can be combined with angiogenic modulating substances, which highlights its potential in the study of angiogenesis with an in vivo perspective.

Purpose: Iris vascular tufts (IVT) are rare biomicroscopic capillary outgrowths from the pupillary margins. Patients are usually asymptomatic until presenting with blurred vision due to spontaneous hyphema or with raised intraocular pressure., Case Report: A 61-year-old woman presented to eye casualty with left eye (LE) blurred vision and discomfort for 1 day. Her external ocular examination was unremarkable and visual acuity was 6/6 in the right eye (RE) and 6/9 in the LE. Biomicroscopic examination revealed a 2-mm hyphema in her LE and bilateral multiple small IVT and active bleeding from IVT at the pupillary margin of the LE at the 5 o'clock position. Diagnosis of LE active bleeding from IVT was made and she underwent argon laser photocoagulation directed at the source of bleeding. The bleeding stopped immediately after the second burn. She was followed up for 3 months; her visual acuity was 6/5 and 6/6 in the RE and LE, respectively, with no further problems., Conclusions: Iris vascular tufts are benign and recurrent hemorrhages are unlikely. Therefore, definitive argon laser photocoagulation or surgical treatment are reserved to arrest further episodes of hyphema. Our case demonstrates the effective use of argon laser photocoagulation to completely arrest active bleeding from IVT and excellent recovery of hyphema with no further problems for 5 years.

Purpose: To evaluate the effects of carotid artery angioplasty and stenting (CAAS) on patients who were diagnosed with ocular ischemic syndrome (OIS)., Methods: Sixty-four eyes of 64 OIS patients with ipsilateral internal carotid artery stenosis ≥70% were included in the study. The study eyes were divided into two groups according to the presence of iris neovascularization: NVI-absent group and NVI-present group, with 32 eyes, respectively. All patients received ocular treatment modality according to the presence of non-perfusion area (pan-retinal photocoagulation) and intraocular pressure (medical treatment included timolol maleate eye drops combined with brinzolamide eye drop; trabeculectomy and cyclophotocoagulation). All patients went through CAAS surgery for treatment of internal carotid artery stenosis. Best-corrected visual acuity (BCVA); intraocular pressure (IOP), slit lamp examination, iris fluorescence angiography, fundus fluorescein angiography and color Doppler ultrasound of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCA) were performed pre-operatively and 1 month, 3 months, 6 months, and 12 months post-operatively., Results: There was no significant BCVA change postoperatively in the NVI-absent group, while postoperative BCVA in the INV-present group decreased significantly. There was no significant BCVA difference at pre-operative and 1month post-operative follow-up between the two groups. However, post-operative BCVA of NVI-present group starting from 3-months follow-up was significantly worse than NVI-absent group. Arm-retinal artery circulation time and arteriovenous circulation time decreased significantly in NVI-absent group, while showed no statistical difference in NVI-present group during the 12-months follow-up. Postoperative peak systolic velocity (PSV) of the ophthalmic artery, the central retinal artery, and short posterior ciliary artery showed significant increases at 1 month, 3 months, 6 months and 12 months follow-up in both groups., Conclusion: CAAS can greatly improve ocular blood in OIS patients with and without iris neovascularization. However, CAAS improved BCVA only in patients without iris neovascularization.

Purpose: The iris allows effective delivery of nutrients into the aqueous humor supplying the surrounded avascular tissues. However, possible underlying mechanisms of the iris vasculature have not been well established. This study aims to quantitatively assess the human iris vascular network, endothelial cell morphometries, and characterize endothelial junctions to better understand the properties of the iris vasculature., Materials and Methods: The irises from human donor eyes were dissected and short fixed before float staining for VE-cadherin and claudin-5, f-actin and nuclei and flat-mounted for confocal imaging. The iris microvasculature was studied for its distribution and branch orders. The endothelial and nuclear morphometrics were measured for each vessel order. Characteristics of cellular junction staining and intracellular cytoskeleton were investigated., Results: The human iris vasculature was found to comprise of six orders of arteries, three orders of veins, and capillaries. The endothelial cell shape was long and narrow in all arteries, suggesting a high hemodynamic shear stress. Relatively large vessels ran radially in the superficial two-thirds of the iris, while smaller and denser vessels ran in the deepest third. Significant heterogeneity in vascular diameter, shape of the endothelia and nuclei, and the nuclear position was evident between artery, capillary and vein. Staining of junction proteins VE-cadherin and claudin-5 appeared non-uniform at the cell borders, especially in large veins., Conclusions: High rates of blood flow and special barrier properties are indicated by the morphological properties of the human iris vasculature. Detailed information of the iris vasculature combined with the inter- and intra-endothelial structure may help us further understand the physiological and pathogenic roles of the iris.

Importance: Optical coherence tomography angiography (OCTA) allows visualization of iris racemose hemangioma course and its relation to the normal iris microvasculature., Objective: To describe OCTA features of iris racemose hemangioma., Design, Setting, and Participants: Descriptive, noncomparative case series at a tertiary referral center (Ocular Oncology Service of Wills Eye Hospital). Patients diagnosed with unilateral iris racemose hemangioma were included in the study., Main Outcomes and Measures: Features of iris racemose hemangioma on OCTA., Results: Four eyes of 4 patients with unilateral iris racemose hemangioma were included in the study. Mean patient age was 50 years, all patients were white, and Snellen visual acuity was 20/20 in each case. All eyes had sectoral iris racemose hemangioma without associated iris or ciliary body solid tumor on clinical examination and ultrasound biomicroscopy. By anterior segment OCT, the racemose hemangioma was partially visualized in all cases. By OCTA, the hemangioma was clearly visualized as a uniform large-caliber vascular tortuous loop with intense flow characteristics superimposed over small-caliber radial iris vessels against a background of low-signal iris stroma. The vascular course on OCTA resembled a light bulb filament (filament sign), arising from the peripheral iris (base of light bulb) and forming a tortuous loop on reaching its peak (midfilament) near the pupil (n = 3) or midzonal iris (n = 1), before returning to the peripheral iris (base of light bulb). Intravenous fluorescein angiography performed in 1 eye depicted the iris hemangioma; however, small-caliber radial iris vessels were more distinct on OCTA than intravenous fluorescein angiography., Conclusions and Relevance: Optical coherence tomography angiography is a noninvasive vascular imaging modality that clearly depicts the looping course of iris racemose hemangioma. Optical coherence tomography angiography depicted fine details of radial iris vessels, not distinct on intravenous fluorescein angiography.

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 mm 2 , and 15.17 ± 1.06°, respectively., Conclusions: Ultrasound biomicroscopy could be a useful diagnostic tool to evaluate anterior ocular segment of pigeons., (© 2017 American College of Veterinary Ophthalmologists.)

Purpose/Aim of the study: To assess the ability of optical coherence tomographic angiography (OCTA) to visualize the normal iris vasculature as well as neovascularization of the iris (NVI)., Materials and Methods: Study participants with healthy eyes, patients at risk of NVI development and patients with active or regressed NVI were consecutively included in this cross-sectional observational study. Imaging was performed using a commercially available OCTA system (RTVue- XR Avanti, Optovue Inc., Fremont, CA, USA). Abnormal iris vessels were graded on OCTA according to a modified clinical staging system and compared to slitlamp and gonioscopic findings., Results: Fifty eyes of 26 study participants (16 healthy eyes, 19 eyes at risk, 15 eyes with different stages of NVI) were imaged using OCTA. In 11 out of 16 healthy eyes (69%) with light or moderately dark iris pigmentation, we observed physiological, radially aligned iris vasculature on OCTA imaging, which could not be visualized in five eyes (31%) with darkly pigmented irides. One eye in the "eyes at risk" group was diagnosed with NVI based on OCTA, which was not observed clinically. Fifteen eyes with clinically active or regressed NVI were imaged. Different stages of NVI could be differentiated by OCTA, corresponding well to an established clinical grading system. Four eyes showed regressed NVI by OCTA, not seen clinically, and were graded as a newly defined stage 4., Conclusions: This pilot clinical study showed that OCTA for imaging of the iris vasculature in health and disease is highly dependent on iris pigmentation. Fine, clinically invisible iris vessels can be visualized by OCTA in the very early stages as well as in the regressed stage of NVI.

Purpose: To assess iris neovascularization by uveal puncture of the mouse eye and determine the role of angiogenic factors during iris neovascularization., Methods: Uveal punctures were performed on BalbC mouse eyes to induce iris angiogenesis. VEGF-blockage was used as an anti-angiogenic treatment, while normoxia- and hypoxia-conditioned media from retinal pigment epithelium (RPE) cells was used as an angiogenic-inducer in this model. Iris vasculature was determined in vivo by noninvasive methods. Iris blood vessels were stained for platelet endothelial cell adhesion molecule-1 and vascular sprouts were counted as markers of angiogenesis. Expression of angiogenic and inflammatory factors in the puncture-induced model were determined by qPCR and western blot., Results: Punctures led to increased neovascularization and sprouting of the iris. qPCR and protein analysis showed an increase of angiogenic factors, particularly in the plasminogen-activating receptor and inflammatory systems. VEGF-blockage partly reduced iris neovascularization, and treatment with hypoxia-conditioned RPE medium led to a statistically significant increase in iris neovascularization., Conclusions: This study presents the first evidence of a puncture-induced iris angiogenesis model in the mouse. In a broader context, this novel in vivo model of neovascularization has the potential for noninvasive evaluation of angiogenesis modulating substances.

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., (© 2016 American College of Veterinary Ophthalmologists.)

Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

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., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this paper was to describe the possible implications of topical (ocular) administration of Metamizole on vascular reactivity of the iris in Wistar rats. No other study regarding its topical use was found. Methods: Male adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight - injected intraperitoneally - while maintaining spontaneous respiration and the blink reflex. After selecting the area of interest (long posterior ciliary artery - LPCA), manual adjustments of the image magnitude, clarity, and brightness were made, and the experiment began. The image recording lasted 10 minutes. Results: Metamizole induced a slight vasoconstriction that started with the initial moment for all the doses used. After the topical administration of Metamizole, we did not observe an increase of the vascular diameter of LPCA in a dose dependent manner. The saline solution used as a negative control did not modify the vessel diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is commonly used in human and veterinary medicine. It is the most popular first-line analgesic in various populations. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy of metamizole, as well as its spasmolytic effect, makes it a very important pharmaceutical agent that could be used in the therapy of various eye disorders in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative diabetic retinopathy.

Uveitis-Glaucoma-Hyphaema Syndrome (UGH syndrome, or "Ellingson" Syndrome) is a rare condition caused by the mechanical trauma of an intraocular lens malpositioned over adjacent structures (iris, ciliary body, iridocorneal angle), leading to a spectrum of iris transillumination defects, microhyphaemas and pigmentary dispersion, concomitant with elevated intraocular pressure (IOP). UGH Syndrome can also be characterized by chronic inflammation, secondary iris neovascularization, cystoid macular edema (CME). The fundamental step in the pathogenesis of UGH syndrome appears to arise from repetitive mechanical iris trauma by a malpositioned or subluxed IOL. These patients have uncomplicated cataract implants and return for episodes of blurry vision weeks to months after surgery. This may be accompanied by pain, photophobia, erythropsia, anterior uveitis, hyphaema along with raised intraocular pressure. A careful history and examination, as well as appropriate investigations can confirm the diagnostic. Treatment options are IOL Explantation exchange, topical and systemic medication, and cyclophotocoagulation, the placement of a Capsular Tension Ring to redistribute zonular tension and Anti-vascular endothelial growth factor (anti-VEGF) Therapy.

Purpose: To investigate the incidence of neovascularization of the iris (NVI) and clinical features of patients with NVI following acute central retinal artery occlusion (CRAO)., Methods: A retrospective review of 214 consecutive CRAO patients who visited one tertiary hospital between January 2009 and January 2015 was conducted. In total, 110 patients were eligible for this study after excluding patients with arteritic CRAO, a lack of follow-up, iatrogenic CRAO secondary to cosmetic filler injection, or NVI detected before CRAO attack. Fluorescein angiography (FA) was applied until retinal arterial reperfusion was achieved, typically within 1 to 3 months., Results: The incidence of NVI was 10.9% (12 out of 110 patients). Neovascular glaucoma was found in seven patients (6.4%). The mean time to NVI diagnosis after CRAO events was 3.0 months (range, 1 week to 15 months). The cumulative incidence was 5.5% at 3 months, 7.3% at 6 months, and 10.9% at 15 months. Severely narrowed ipsilateral carotid arteries were observed in only three patients (27.3%). The other nine patients (75.0%) showed no predisposing conditions for NVI, such as proliferative diabetic retinopathy or central retinal vein occlusion. Reperfusion rate and prevalence of diabetes were significantly different between patients with NVI and patients without NVI (reperfusion: 0% [NVI] vs. 94.7% [no NVI], p < 0.001; diabetes: 50.0% [NVI] vs. 17.3% [no NVI], p = 0.017)., Conclusions: CRAO may lead to NVI and neovascular glaucoma caused by chronic retinal ischemia from reperfusion failure. Our results indicate that follow-up fluorescein angiography is important to evaluate retinal artery reperfusion after acute CRAO events, and that prophylactic treatment such as panretinal photocoagulation should be considered if retinal arterial perfusion is not recovered., Competing Interests: No potential conflict of interest relevant to this article was reported.

Case Report: A 50-year-old patient was seen during a regular follow up. The main complaint was decreased near-sight vision. Biomicroscopy showed a vascular malformation on the temporal sector of the iris in the left eye, diagnosed as an arteriovenous malformation. A second case of similar features is also presented., Discussion: The vascular malformations of the iris may be asymptomatic and go unnoticed or cause recurrent spontaneous hyphemas. Treatment must be individualised and may range from observation to photocoagulation with laser, or even surgery., (Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

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.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background/aims: To clinically characterise corneal neovascularisation (CVas) with a view to elaborate clinical presentations and to standardise descriptors for clinical evaluation and research., Methods: Corneas of 165 patients with CVas due to a variety of corneal pathologies were observed clinically with the slit lamp biomicroscope and photography at different time points over the course of their disease. Parameters assessed included location, depth, length, branching pattern, colour, lipid leakage, nature of blood flow and presence of haemorrhage. A clinical grading of CVas was applied., Results: CVas can arise from the limbus, conjunctiva and iris. CVas preferentially travels along planes created by corneal incisions, suture tracks and lamellar keratoplasty, both deep lamellar and endothelial keratoplasty. CVas also principally follows the depth of pathology. CVas can be classified into active young, active old, mature, partially regressed and regressed. Herpetic infection was the most common cause of lipid keratopathy. Acanthamoeba keratitis induced the least amount of vascularisation. A simple and efficient clinical grading system for ascertaining the severity of CVas was developed and validated., Conclusions: The various clinical characteristics of CVas described in this study can be used to standardise the nomenclature and description of CVas and clinically grade its severity. As modern, effective methods of treating CVas are being introduced, it is important that there is uniformity in the descriptors used to establish baseline values and evaluate outcomes of treatment. The parameters established in this study can help in this regard., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)