Intravitreal Bevacizumab for Inflammatory Neovascularization of the Lens after Traumatic Open Globe Injury.

To describe a case of inflammatory neovascularization of the lens after open globe injury.Case report.A 57-year-old man presented with severe inflammation, posterior synechiae with traumatic cataract, and thick neovascularization of the intralenticular and anterior lens capsule after open globe injury in the left eye. We administered an intravitreal bevacizumab injection and performed cataract surgery with synechiolysis 1 month later.Inflammation after open globe injury may present as intralenticular neovascularization. Before cataract surgery for traumatic cataract with intralenticular neovascularization, the use of intravitreal bevacizumab injection was ineffective.

Why Is Very High Cholesterol Content Beneficial for the Eye Lens but Negative for Other Organs?

The plasma membranes of the human lens fiber cell are overloaded with cholesterol that not only saturates the phospholipid bilayer of these membranes but also leads to the formation of pure cholesterol bilayer domains. Cholesterol level increases with age, and for older persons, it exceeds the cholesterol solubility threshold, leading to the formation of cholesterol crystals. All these changes occur in the normal lens without too much compromise to lens transparency. If the cholesterol content in the cell membranes of other organs increases to extent where cholesterol crystals forma, a pathological condition begins. In arterial cells, minute cholesterol crystals activate inflammasomes, induce inflammation, and cause atherosclerosis development. In this review, we will indicate possible factors that distinguish between beneficial and negative cholesterol action, limiting cholesterol actions to those performed through cholesterol in cell membranes and by cholesterol crystals.

A Bidomain Model for Lens Microcirculation.

There exists a large body of research on the lens of the mammalian eye over the past several decades. The objective of this work is to provide a link between the most recent computational models and some of the pioneering work in the 1970s and 80s. We introduce a general nonelectroneutral model to study the microcirculation in the lens of the eye. It describes the steady-state relationships among ion fluxes, between water flow and electric field inside cells, and in the narrow extracellular spaces between cells in the lens. Using asymptotic analysis, we derive a simplified model based on physiological data and compare our results with those in the literature. We show that our simplified model can be reduced further to the first-generation models, whereas our full model is consistent with the most recent computational models. In addition, our simplified model captures in its equations the main features of the full computational models. Our results serve as a useful link intermediate between the computational models and the first-generation analytical models. Simplified models of this sort may be particularly helpful as the roles of similar osmotic pumps of microcirculation are examined in other tissues with narrow extracellular spaces, such as cardiac and skeletal muscle, liver, kidney, epithelia in general, and the narrow extracellular spaces of the central nervous system, the "brain." Simplified models may reveal the general functional plan of these systems before full computational models become feasible and specific.

Posterior lenticonus with persistent fetal vasculature.

A 10 year old girl present with both eyes central cataract with posterior lenticonus. Intraoperative, she was noted to have both eyes persistent fetal vasculature (PFV). To the best of our knowledge, association of bilateral posterior lenticonus and PFV has not been reported before. This supports the hypothesis that PFV has a role in pathogenesis of posterior lenticonus.

The lens internal microcirculation system delivers solutes to the lens core faster than would be predicted by passive diffusion.

It has been proposed that optical properties of the lens are actively maintained by an internal microcirculation system that utilizes ionic and fluid fluxes to deliver nutrients to deeper regions of the lens tissue via the extracellular space faster than would occur by passive diffusion alone. To test this hypothesis, we utilized a range of commercially available magnetic resonance imaging (MRI) reagents of varying molecular sizes that served as tracers of extracellular solute delivery. The penetration of these tracers into bovine lenses incubated in the absence and presence of solutions that inhibit the microcirculation was monitored in real time over a 4-h period using T1-weighted MRI. We found that only the smaller contrast agents were delivered to the core of the lens and that the rate of solute penetration was significantly faster than that calculated simple diffusion. Next, the lenses were first incubated in either high extracellular K+ to depolarize the lens potential or ouabain to inhibit the Na+ pump. These two perturbations are known to inhibit the circulating ionic and fluid fluxes that are proposed to drive solute delivery into the lens core. Both perturbations inhibited the delivery of the extracellular tracer molecules to the lens core. Our findings suggest that the microcirculation system can potentially be harnessed to deliver exogenous antioxidants to the lens core to afford mature fiber cells protection against oxidative damage that ultimately manifests as age-related nuclear cataract.

Ocular vessel patterning in zebrafish is indirectly regulated by Hedgehog signaling.

The superficial ocular vasculature of the embryonic zebrafish develops in a highly stereotypic manner and hence provides a convenient model for studying molecular mechanisms that regulate vascular patterning. We have used transgenic zebrafish embryos in which all endothelial cells express enhanced Green Fluorescent Protein and small molecule inhibitors to examine the contribution of two signaling pathways, vascular endothelial growth factor (VEGF) and Hedgehog (Hh) pathways, to the development of the superficial system. We find that most, but not all vessels of the superficial system depend on VEGF signaling for their growth. Hh signaling appears to limit superficial vessel growth over the dorsal eye and is required to promote superficial vessel growth over the ventral eye. These effects of Hh signaling are indirect. Our initial analyses of factors that regulate growth and patterning of superficial ocular vessels suggest that early patterning events in the embryo during organogenesis stages could influence vascular patterning later on. By studying development of specific vascular systems it should be possible to identify new roles for signaling pathways in regulating vascular development.

Review of the Experimental Background and Implementation of Computational Models of the Ocular Lens Microcirculation.

Our sense of vision is critically dependent on the clarity of the crystalline lens. The most common cause of transparency loss in the lens is age-related nuclear cataract, which is due to accumulative oxidative damage to this tissue. Since the ocular lens is an avascular tissue, it has to maintain its physiological homeostasis and antioxidant levels using a system of water microcirculation. This system has been experimentally imaged in animal lenses using different modalities. Based on these data, computational models have been developed to predict the properties of this system in human lenses and its changes due to aging. Although successful in predicting many aspects of lens fluid dynamics, at least in animal models, these in-silica models still need further improvement to become more accurate and representative of human ocular lens. We have been working on gathering experimental data and simultaneously developing computational models of lens microcirculation for the past decade. This review chronologically looks at the development of data-driven computational foundations of lens microcirculation model, its current state, and future advancement directions. A comprehensive model of lens fluid dynamics is essential to understand the physiological optics of this tissue and ultimately the underlying mechanisms of cataract onset and progression.

Posterior tunica vasculosa lentis and "brittle star" of persistent fetal vasculature.

A 17-month-old girl referred for a suspected ciliary body medulloepithelioma was found to have persistent fetal vasculature. Fluorescein angiography showed perfused hyaloid artery posterior tunica vasculosa lentis with brittle star appearance and nonperfused anterior pupillary membrane. Ultrasound biomicroscopy confirmed absence of iris or ciliary body solid tumor.

Sema3A maintains corneal avascularity during development by inhibiting Vegf induced angioblast migration.

Corneal avascularity is important for optical clarity and normal vision. However, the molecular mechanisms that prevent angioblast migration and vascularization of the developing cornea are not clear. Previously we showed that periocular angioblasts and forming ocular blood vessels avoid the presumptive cornea despite dynamic ingression of neural crest cells. In the current study, we investigate the role of Semaphorin3A (Sema3A), a cell guidance chemorepellent, on angioblast migration and corneal avascularity during development. We show that Sema3A, Vegf, and Nrp1 are expressed in the anterior eye during cornea development. Sema3A mRNA transcripts are expressed at significantly higher levels than Vegf in the lens that is positioned adjacent to the presumptive cornea. Blockade of Sema3A signaling via lens removal or injection of a synthetic Sema3A inhibitor causes ectopic migration of angioblasts into the cornea and results in its subsequent vascularization. In addition, using bead implantation, we demonstrate that exogenous Sema3A protein inhibits Vegf-induced vascularization of the cornea. In agreement with these findings, loss of Sema/Nrp1 signaling in Nrp1(Sema-) mutant mice results in ectopic angioblasts and vascularization of the embryonic mouse corneas. Altogether, our results reveal Sema3A signaling as an important cue during the establishment of corneal avascularity in both chick and mouse embryos. Our study introduces cornea development as a new model for studying the mechanisms involved in vascular patterning during embryogenesis and it also provides new insights into therapeutic potential for Sema3A in neovascular diseases.

Remnants of the anterior tunica vasculosa lentis and long anterior lens zonules.

PURPOSE: To investigate presence of remnants of the tunica vasculosa lentis, a possible indication of anterior segment dysgenesis, in subjects with the long anterior zonule (LAZ) trait. METHODS: Retroillumination photographs of the pupil region had been collected in earlier study of the LAZ trait in African Americans. Secondary image analysis was performed to assess the frequency of intact persistent pupillary membrane iris strands (PPMIS). RESULTS: The analysis included 148 subjects, comprised of 74 LAZ subjects (median age=70 y; range, 50 to 91 y; 64 females) and 74 controls (68 y; 50 to 83 y; 64 females). While controlling for age and sex, analysis showed that LAZ subjects were 3.1 times more likely than controls (odds ratio=3.1; 95% confidence interval, 1.4-6.7; P=0.004) to exhibit PPMIS in at least one of their eyes. CONCLUSION: The LAZ trait, which is being studied as a potential risk factor for glaucoma, was associated with presence of PPMIS in our study population.

[Combined central retinal artery and vein occlusion secondary to cataract surgery in a patient with persistent hyaloid artery]. / Oclusión combinada de arteria y vena central de la retina tras cirugía de catarata en paciente con arteria hialoidea persistente.

CASE REPORT: A 72 year-old woman referred for cataract surgery in her right eye. Biomicroscopy revealed a retrocapsular fibrotic tissue in communication with the optic nerve, suggesting a persistent hyaloid artery (PAH). A posterior capsule rupture unexpectedly occurred during lens hydrodissection. One day after surgery, fundus examination showed a combined central retinal artery and vein occlusion. CONCLUSION: PAH is uncommon, but its presence may alert us of this possible complication during cataract surgery.

A computer model of lens structure and function predicts experimental changes to steady state properties and circulating currents.

BACKGROUND: In a previous study (Vaghefi et al. 2012) we described a 3D computer model that used finite element modeling to capture the structure and function of the ocular lens. This model accurately predicted the steady state properties of the lens including the circulating ionic and fluid fluxes that are believed to underpin the lens internal microcirculation system. In the absence of a blood supply, this system brings nutrients to the core of the lens and removes waste products faster than would be achieved by passive diffusion alone. Here we test the predictive properties of our model by investigating whether it can accurately mimic the experimentally measured changes to lens steady-state properties induced by either depolarising the lens potential or reducing Na+ pump rate. METHODS: To mimic experimental manipulations reported in the literature, the boundary conditions of the model were progressively altered and the model resolved for each new set of conditions. Depolarisation of lens potential was implemented by increasing the extracellular [K+], while inhibition of the Na+ pump was stimulated by utilising the inherent temperature sensitivity of the pump and changing the temperature at which the model was solved. RESULTS: Our model correctly predicted that increasing extracellular [K+] depolarizes the lens potential, reducing and then reversing the magnitude of net current densities around the lens. While lowering the temperature reduced Na+ pump activity and caused a reduction in circulating current, it had a minimal effect on the lens potential, a result consistent with published experimental data. CONCLUSION: We have shown that our model is capable of accurately simulating the effects of two known experimental manipulations on lens steady-state properties. Our results suggest that the model will be a valuable predictive tool to support ongoing studies of lens structure and function.

Alterations of the tunica vasculosa lentis in the rat model of retinopathy of prematurity.

PURPOSE: To study the relationship between retinal and tunica vasculosa lentis (TVL) disease in retinopathy of prematurity (ROP). Although the clinical hallmark of ROP is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. METHODS: ROP was induced in Long-Evans pigmented and Sprague Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope near the height of retinal vascular disease, ~20 days of age, and again at 30 and 64 days of age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (Gelman et al. in Invest Ophthalmol Vis Sci 46:4734-4738, 2005). RESULTS: In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats, it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave, and oscillatory potentials were attenuated in ROP rats. CONCLUSIONS: These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye.

Fugo blade-assisted lens aspiration in a case of intra- and retro-lenticular hemorrhage.

Hemorrhage into the crystalline lens is exceedingly rare but has been described following ocular trauma [1, 2], glaucoma surgery [3-5], laser iridotomy [6], pediatric cataract surgery [7], and also in the absence of an obvious pathology [8]. We describe a case of intra- and retro-lenticular organised bleed which presented 9 years following repair of open globe injury and which was treated using fugo blade-assisted lens aspiration. The fugo blade provided adequate endocoagulation of retrolenticular blood during posterior capsulotomy and prevented undue anterior segment hemorrhage.

Dramatic regression of persistent tunica vasculosa lentis associated with retinopathy of prematurity following treatment with intravitreal bevacizumab.

The authors describe a preterm infant who developed advanced retinopathy of prematurity bilaterally with a prominent tunica vasculosa lentis. Treatment with intravitreal bevacizumab resulted in regression of the tunica vasculosa lentis and posterior manifestations of the retinopathy of prematurity. RetCam imaging (Clarity Medical Systems, Pleasanton, CA) of the anterior segment was used to document the dramatic tunica vasculosa lentis resolution.

Intralenticular neovascularization in a cataractous crystalline lens.

BACKGROUND: Neovascularization can occur in various ocular structures including the retina, iris, anterior chamber angle and cornea; however, it rarely occurs in the crystalline lens. Neovascularization results secondary to hypoxic conditions within the eye. A natural balance of angiogenic and antiangiogenic factors are critical for the eye to prevent the formation of neovascularization. Various factors can upset this natural balance, resulting in angiogenesis. Due to the lack of an intrinsic blood supply, intralenticular neovascularization is rare. CASE REPORT: A 61-year-old black male presented with a previous diagnosis of proliferative diabetic retinopathy (PDR). His ocular history included cataract extraction in the left eye (OS) and tractional retinal detachment in both eyes that was surgically repaired OS. His entering visual acuities were NLP OD and 20/400 OS. Upon biomicroscopic evaluation OD, there was evidence of a hypermature cataract with iris neovascularization and neovascularization coursing over and within the anterior capsule of the lens. CONCLUSIONS: Intralenticular neovascularization is a rarely reported ocular complication. We present a patient with uncontrolled diabetes resulting in proliferative diabetic retinopathy, extreme ocular ischemia, and consequent intralenticular neovascularization.