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.

The use of optical coherence tomography angiography to measure changes in iris vasculature after strabismus surgery.

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.

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.

Urrets-Zavalia syndrome following cataract surgery in dogs: A case series.

Background: In human medicine, Urrets-Zavalia syndrome (UZS) is a well-recognized but uncommon postoperative complication characterized by a fixed dilated pupil, accompanied by iris atrophy and glaucoma. Although it was originally reported in 1963 after penetrating keratoplasty surgery for keratoconus, it has been associated with various ophthalmic procedures such as cataract surgery. The condition has not been previously published in the veterinary literature. Case Description: Three client-owned diabetic dogs that developed UZS´s triad after cataract surgery are described. Despite uneventful phacoemulsification in the six eyes, five developed moderate-to-severe postoperative ocular hypertension. Although intraocular pressure (IOP) spikes were initially controlled, fixed dilated pupils accompanied by iris atrophy and chronic ocular hypertension were seen in the five affected eyes. Aggressive medical and surgical management maintained vision in three of those eyes. In one eye, uncontrolled IOP led to blindness. Conclusion: This is the first published description of UZS in dogs, occurring after phacoemulsification. Although no exact, demonstrable causative element could be determined, we believe that should be considered a triggering condition for this syndrome, as it directly affects the ocular blood flow autoregulation and intrinsic uveal tissue integrity. Until the contrary is proved, diabetes mellitus might be considered as a risk factor for developing this syndrome after cataract surgery in dogs.

Optical coherence tomography angiography application to pigmented iris: Could a new index quantify blood flow?

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.

Dendritic cells play no significant role in the laser-induced choroidal neovascularization model.

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.

Anterior segment optical coherence tomography angiography for iris vasculature in pigmented eyes.

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.

The efficacy and safety of intravitreal conbercept combined with mitomycin C augmented trabeculectomy for treating neovascular glaucoma.

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.

Aqueous Inflammation and Ischemia-Related Biomarkers in Neovascular Glaucoma with Stable Iris Neovascularization.

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.

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.

Spontaneous microscopic hyphema secondary to iris vascular tufts: Case report with video documentation.

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).

Predictors of enucleation in Coats disease: analysis of 259 eyes of 259 patients at a single center.

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.

Observation of treated iris neovascularization by swept-source-based en-face anterior-segment optical coherence tomography angiography.

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.

The effects of prostaglandins and endocannabinoids on iris arterial vascularization in Wistar rats - Experimental analysis.

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).

Blood Vessels and Lymphatic Vessels in the Cornea and Iris After Penetrating Keratoplasty.

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.

Iris varix: 10-year experience with 28 eyes.

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.