Improvement of Uveal and Capsular Biocompatibility of Hydrophobic Acrylic Intraocular Lens by Surface Grafting with 2-Methacryloyloxyethyl Phosphorylcholine-Methacrylic Acid Copolymer.

Biocompatibility of intraocular lens (IOL) is critical to vision reconstruction after cataract surgery. Foldable hydrophobic acrylic IOL is vulnerable to the adhesion of extracellular matrix proteins and cells, leading to increased incidence of postoperative inflammation and capsule opacification. To increase IOL biocompatibility, we synthesized a hydrophilic copolymer P(MPC-MAA) and grafted the copolymer onto the surface of IOL through air plasma treatment. X-ray photoelectron spectroscopy, atomic force microscopy and static water contact angle were used to characterize chemical changes, topography and hydrophilicity of the IOL surface, respectively. Quartz crystal microbalance with dissipation (QCM-D) showed that P(MPC-MAA) modified IOLs were resistant to protein adsorption. Moreover, P(MPC-MAA) modification inhibited adhesion and proliferation of lens epithelial cells (LECs) in vitro. To analyze uveal and capsular biocompatibility in vivo, we implanted the P(MPC-MAA) modified IOLs into rabbits after phacoemulsification. P(MPC-MAA) modification significantly reduced postoperative inflammation and anterior capsule opacification (ACO), and did not affect posterior capsule opacification (PCO). Collectively, our study suggests that surface modification by P(MPC-MAA) can significantly improve uveal and capsular biocompatibility of hydrophobic acrylic IOL, which could potentially benefit patients with blood-aqueous barrier damage.

Pharmacological Actions of Hydrogen Sulfide Donors on Sympathetic Neurotransmission in the Bovine Anterior Uvea, In Vitro.

In the present study, we investigated the effect of three different sources of hydrogen sulfide (H2S) on sympathetic neurotransmission from isolated superfused bovine iris-ciliary bodies. The three agents under consideration were: ACS67, a hybrid of latanoprost and a H2S-donating moiety; L-cysteine, a substrate for endogenous production of H2S and GYY 4137, a slow donor of H2S. We also examined the contribution of prostaglandins to the pharmacological actions of the H2S donors on release of [(3)H]-norepinephrine ([(3)H]NE) triggered by electrical field stimulation. ACS67, L-cysteine and GYY 4137 caused a concentration-dependent inhibition of electrically-evoked [(3)H]NE release from isolated bovine iris-ciliary bodies without affecting basal [(3)H]NE efflux. The cyclooxygenase inhibitor, flurbiprofen enhanced the inhibitory action of ACS67 and L-cysteine on stimulated [(3)H]NE release. Both aminooxyacetic acid, an inhibitor of cystathionine-ß-synthase and glibenclamide, a KATP channel blocker reversed the inhibition of evoked NE release induced by the H2S donors. We conclude that H2S donors can inhibit sympathetic neurotransmission from isolated bovine iris-ciliary bodies, an effect partially dependent on the in situ production of H2S and prostanoids, and is mediated by an action on KATP channels.

Evaluation of uveal and capsule biocompatibility of a single-piece hydrophobic acrylic intraocular lens with ultraviolet-ozone treatment on the posterior surface.

PURPOSE: To evaluate a single-piece hydrophobic acrylic intraocular lens (IOL) with ultraviolet-ozone (UV-O3) treatment on the posterior surface and compare it with an identical untreated IOL in a rabbit model. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Study IOLs were implanted in the right eyes and control IOLs in the left eyes of 10 New Zealand rabbits. Slitlamp examinations were performed 1 to 6 weeks postoperatively. Neodymium:YAG (Nd:YAG) posterior capsulotomy was performed in both eyes of 5 rabbits after the 4-week slitlamp examination. At 6 weeks, the rabbits were killed humanely and their globes were enucleated. Capsular bag opacification was scored from the posterior aspect (Miyake-Apple view), and the eyes were processed for histopathology. RESULTS: At 4 weeks, the mean posterior capsule opacification (PCO) scores were 0.88 ± 0.33 (SD) in the study eyes and 2.55 ± 1.13 in the control eyes (P=.003, 2-tailed paired t test). Performance of Nd:YAG posterior capsulotomy was similar in both groups. Gross postmortem examination also showed statistically less peripheral PCO in eyes with the study IOLs than in control eyes. There was no difference in histopathologic findings between study eyes and control eyes and no signs of untoward inflammation or toxicity in any eye evaluated. CONCLUSIONS: Treatment of the posterior surface of a single-piece hydrophobic acrylic IOL with UV-O3 appears to prevent PCO, likely by increasing adhesion between the posterior capsule and the IOL while retaining uveal biocompatibility. Performance of Nd:YAG posterior capsulotomy was similar between treated IOLs and untreated IOLs.

Estudio mediante biomicroscopia ultrasónica de pacientes intervenidos de esclerectomía profunda no perforante con implante supraciliar / An ultrasound biomicroscopy study after deep sclerectomy with supraciliary implant

OBJETIVO: Evaluar a pacientes 24 meses después de ser intervenidos mediante esclerectomía profunda no perforante (EPNP) con implante supraciliar y determinar la existencia de factores predictivos de la eficacia de la técnica mediante la exploración biomicroscópica (BMU). MATERIAL Y MÉTODOS: Se incluyen 26 ojos de 23 pacientes explorados con UBM 24 meses después de ser intervenidos mediante EPNP con implante de hema supraciliar. RESULTADOS: Se ha encontrado un descenso significativo de la presión intraocular (PIO) de 25,6 ± 6,4 mmHg a 16,2 ± 3,4 mmHg y en el número de medicaciones antiglaucomatosas de 2,5 ± 0,6 por paciente a 0,5 ± 0,5 (p < 0,001). No se evidenciaron cambios significativos en la agudeza visual. Mediante BMU no se ha podido correlacionar la PIO con el diámetro horizontal (r = −0,05; p = 0,71) ni vertical (r = −0,1; p = 0,63) del lago intraescleral, su altura (r = 0,28; p = 0,25) ni volumen (r = −0,08; p = 0,79), el grosor de la MBTD (r = −0,07; p = 0,73) ni su longitud (r = 0,39; p = 0,13), la presencia de ampolla filtrante (p = 0,3) ni de un área hipogénica en el espacio supracoroideo (p = 0,2). CONCLUSIONES: La inserción del implante de hema en el espacio supraciliar durante la cirugía no perforante del glaucoma es segura y efectiva en el glaucoma de ángulo abierto (GAA) pero no hemos podido establecer factores

OBJETIVE: To evaluate patients 24 months after deep sclerectomy (DE) with supraciliary implant, and identify any predictive success factors by examination with ultrasound biomicroscopy (UBM). MATERIAL AND METHODS: This study included 26 eyes of 23 patients evaluated by UBM 24 months after a deep sclerectomy with a supraciliary hema implant. RESULTS: There was a significant reduction in intraocular pressure (IOP), changing from a preoperative mean of 25.6 ± 6.4 mmHg to a postoperative mean of 16.2 ± 3.4 mmHg (P<.001). The number of preoperative glaucoma medications also decreased from 2.5 ± 0.6 drugs per patient to 0.5 ± 0.5 (P<.001). No change was observed in the best-corrected visual acuity. The anatomical characteristics of the surgical area, and its relationship with IOP were examined using UBM. There was no correlation between the level of IOP at the time of UBM and the horizontal (r=−.05: P=.71) and vertical diameter (r=−.1; P=.63), the height (r=.28; P=.25) and the volume of intrascleral space (r=−.08; P=.79), the thickness (r=−.07;P=.73) and the length (r=.39; P=.13) of trabeculo-Descemet's membrane (TDM), the presence of filtering bleb (P=.30) and the hypoechoic area in the supraciliary space (P=.24). CONCLUSIONS: The insertion of a hema implant in the supraciliary space is an effective and safe surgery for patients with open angle glaucoma (OAG). No predictive success factors for supraciliary implant were found using the UBM study

The effects of tenascin C knockdown on trabecular meshwork outflow resistance.

PURPOSE: Tenascin C (TNC) is a matricellular glycoprotein whose expression in adult tissue is indicative of tissue remodeling. The purpose of the current study was to determine the localization of TNC in trabecular meshwork (TM) tissue and to analyze the effects of TNC on intraocular pressure (IOP). METHODS: Human TM frontal sections were immunostained with anti-TNC and imaged by confocal microscopy. TNC mRNA and protein levels were quantitated in anterior segments perfused at physiological and elevated pressure. Short, hairpin RNA (shRNA) silencing lentivirus targeting full-length TNC (shTNC) was applied to anterior segment perfusion organ cultures. The IOPs and central corneal thickness (CCT) of wild-type, TNC(-/-), and tenascin X (TNX(-/-)) knockout mice were measured. RESULTS: TNC was distributed in the juxtacanalicular (JCT) region of adult human TM, predominantly in the basement membrane underlying the inner wall of Schlemm's canal. Application of shTNC lentivirus to human and porcine anterior segments in perfusion culture did not significantly affect outflow rate. Although TNC was upregulated in response to pressure, there was no difference in outflow rate when shTNC-silenced anterior segments were subjected to elevated pressure. Furthermore, IOPs and CCTs were not significantly different between TNC(-/-) or TNX(-/-) and wild-type mice. CONCLUSIONS: TNC does not appear to contribute directly to outflow resistance. However, TNC immunolocalization in the JCT of adult human eyes suggests that certain areas of the TM are being continuously remodeled with or without an IOP increase.

Aqueous humor dynamics during the day and night in juvenile and adult rabbits.

PURPOSE: To determine the day and night differences in intraocular pressure (IOP), aqueous flow, outflow facility, uveoscleral outflow, and central corneal thickness (CCT) in juvenile and adult rabbits. METHODS: Studies were performed on twelve 3-month-old and ten 12-month-old male New Zealand White rabbits. Daytime measurements were made between 9 AM (3 hours after lights on) and 3 PM, and nighttime measurements were made between 11 PM and 5 AM. IOP was measured by pneumotonometry and aqueous flow by fluorophotometry. Outflow facility was determined by both fluorophotometry and tonography. Uveoscleral outflow was calculated by the Goldmann equation. CCT was measured by ultrasound pachymetry. Repeated-measures ANOVAs and Student's two-tailed t-tests were used for statistical comparisons. RESULTS: When nighttime versus daytime readings were compared, IOP, aqueous flow and uveoscleral outflow were higher, fluorophotometric outflow facility was lower, and CCT was thinner in both age groups. When the juvenile rabbits were compared to adult rabbits, IOP was lower, aqueous flow and uveoscleral outflow were higher, and fluorophotometric outflow facility and CCT were not different during the day or night. Tonographic outflow facility did not change in a 24-hour period in the juvenile rabbits. CONCLUSIONS: The increased IOP at night in rabbits can be explained mainly by a decrease in outflow facility. An increase in aqueous flow at night is counterbalanced by an increase in uveoscleral outflow. Although the rates of aqueous flow and uveoscleral outflow slow with maturity, their relative day/night differences remain the same.

Canine anterior uveitis.

Canine anterior uveitis can be a debilitating, painful, vision-threatening disease. Several local and systemic diseases can cause anterior uveitis. Because the eye is limited in its ability to respond to injury, different diseases produce similar clinical signs, making an etiologic diagnosis difficult but imperative to improve the likelihood of a successful outcome. A thorough history and complete ocular and physical evaluations are necessary to ensure timely and accurate diagnosis. This article reviews the pathophysiology, most common causes, diagnostic recommendations, current therapeutic options, potential complications, and prognosis for canine anterior uveitis.

Uveoscleral outflow--a review.

The uveoscleral outflow route was described more than 40 years ago. Part of aqueous leaves the eye through the iris root. The ciliary muscle, and there are large species differences in the fraction of aqueous outflow that leaves the eye through this route. In non-human primates 40-50% of aqueous leaves the eye by the uveoscleral route. In human eyes most data has been collected by indirect calculations, with results suggesting a similar fraction, at least in eyes from younger individuals. An age-dependent reduction in uveoscleral flow in human eyes may explain the initial difference seen between non-human primate and human eyes. Unlike trabecular outflow, intraocular pressures within the normal range have little effect on uveoscleral outflow. This may be explained by the fact that changes in intraocular pressure have little effect on the pressure gradient for flow through the ciliary muscle, which is likely to be the rate-limiting step in uveoscleral outflow. The state of the ciliary muscle is important and contraction reduces while relaxation increases uveoscleral flow. Similar effects are achieved with cholinergic agonists and antagonists. Epinephrine increases uveoscleral flow, most likely through stimulating beta(2)-adrenergic receptors. Prostaglandin F(2alpha) and prostaglandin F(2alpha)-analogues effectively reduce intraocular pressure by increasing uveoscleral flow. This is mediated by structural changes in the extracellular matrix of the ciliary muscle, and is likely to contribute to a valuable excess route for aqueous and proteins during intraocular inflammation. Whether uveoscleral flow plays a significant role in any other eye disease is not clear. Thus, 40 years later we are able to successfully increase aqueous flow through the uveoscleral route, a valuable contribution to glaucoma treatment, but we still have only a limited understanding on its physiological role.

Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments.

Monocytes of bone marrow (BM) origin are circulating precursors that replenish dendritic cells and macrophage populations in peripheral tissues during homeostasis. The eye provides a unique range of varying tissue microenvironments in which to compare the different turnover rates of monocyte-derived cells. This was investigated in the present study using radiation chimeras, whereby BM from Cx3cr1(+/gfp) mice was used to rescue myeloablated wild-type (WT) BALB/c mice (conventional chimeras). The use of Cx3cr1(+/gfp) mice as BM donors allowed the clear visualization of newly recruited monocyte-derived cells. Following BM reconstitution, mice were killed at 2, 4, 6, and 8 weeks, and wholemount ocular tissues were processed for immunohistochemistry and confocal microscopy. "Reverse" chimeras (WT into Cx3cr1(+/gfp)) were also created to act as a further method of cross-referencing cell turnover rates. In conventional chimeras, Cx3cr1(+/gfp) cells began repopulating the uveal tract (iris, ciliary body, choroid) 2 weeks post-transplantation with close to complete replenishment by 8 weeks. By contrast, the earliest recruitment of Cx3cr1(+/gfp) cells into the host retina occurred at 4 weeks. In reverse chimeras, a steady accumulation of host Cx3cr1(+/gfp) macrophages in the subretinal space of Cx3cr1(+/gfp) adult mice suggests that these cells arise from long-term resident microglia and not newly recruited WT donor cells. In summary, chimeric mouse models, in which lineage-specific cells carry a fluorescent reporter, have been used in the present study to visualize the turnover of monocyte-derived cells in different tissue compartments of the eye. These data provide valuable insights into differential monocyte turnover rates within a single complex organ.

Uveal and capsular biocompatibility after implantation of sharp-edged hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses in eyes with pseudoexfoliation syndrome.

PURPOSE: To evaluate the uveal and capsular biocompatibility of 3 types of sharp-edged foldable intraocular lenses (IOLs) in eyes with pseudoexfoliation syndrome (PEX). SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Eighty-five eyes with PEX had implantation of 1 of the following sharp-edged 3-piece IOLs: hydrophilic acrylic (Injectacryl F3000, OphthalMed), hydrophobic acrylic (AcrySof MA60MB, Alcon), or silicone (CeeOn 911, AMO). Postoperative evaluation (flare, cellular reaction, and capsular reaction) was performed at 1, 3, and 7 days as well as 1, 3, 6, and 12 to 18 months. RESULTS: One year after surgery, flare was comparable between the IOLs. In terms of uveal biocompatibility, whereas the Injectacryl had the highest deposition of debris on the IOL surface (P = .04), the CeeOn 911 had significantly more small round cells in the first 6 months (P<.03). The AcrySof had the highest number of foreign-body giant cells (P = .01). In terms of capsular biocompatibility, lens epithelial cell outgrowth was highest in the AcrySof group (P<.02). Anterior capsule opacification was comparable between the 3 groups. Posterior capsule opacification was mild in all groups but was significantly greater in the Injectacryl group (P<.05). There were no cases of clinically significant IOL decentration or capsule contraction. CONCLUSIONS: In general, inflammatory cells accumulated more easily on hydrophobic IOLs than on hydrophilic IOLs; the AcrySof IOL had the highest prevalence of foreign-body giant cells. All 3 IOLs had good biocompatibility, although the AcrySof group had increased inflammatory signs.

Distribución por edades del melanoma de úvea y su relación con la supervivencia / Age distribution of uveal melanoma and its relationship to survival

Propósito: Estudiar la distribución por edades del melanoma de úvea y relacionarlo con la supervivencia Método: Se ha realizado un estudio retrospectivo en pacientes diagnosticados de melanoma de úvea. Se han analizado entre otras las variables clínicas: edad, sexo, origen y tamaño tumoral, tiempo de seguimiento, estado sistémico actual, fecha y causa de muerte. Resultados: Se han estudiado 303 pacientes afectos de melanoma de úvea. La edad media de los pacientes fue de 60,09 años. La supervivencia en los pacientes = 50 años a los 2, 5 y 10 años es del 90,86%, 73,18% y 58,28% respectivamente, diferencia no estadísticamente significativa entre estos dos grupos de edad. Cuando consideramos el factor sexo en los pacientes >= 50 años encontramos una mayor supervivencia entre los hombres respecto a las mujeres (logrank; p=0,038). Conclusiones: El melanoma de úvea en nuestro medio sigue un patrón de distribución por edades muy similar al descrito en otras series de otros países, no siendo infrecuente el diagnóstico en pacientes jóvenes = 50 años

Purpose: To study the age distribution and survival in patients with uveal melanoma. Methods: A retrospective study was performed on 303 patients diagnosed with uveal melanoma. We analysed the clinical characteristics: age, gender, tumor size and origin, follow-up time, systemic state, survival time and cause of death. Results: The median age of the patients was 60.09 years. The 2-, 5-, and 10-year survival of patients less than 50 years of age at diagnosis was 91.41%, 81.83% and 61.45% respectively. The 2-, 5- and 10- year survival of patients equal to or older than 50 years was 90.86%, 73.18% and 58.28% respectively. No significant difference was found between these two age groups. When we considered a possible relationship between the sex factor and survival, in patients equal to or older than 50 years of age, we found a higher survival in men than in women (logrank test; p=0.038). Conclusions: Uveal melanoma in Spain has a similar age distribution to that of other countries, and it is not an infrequent diagnosis in patients under 40 years of age. Survival rates are also similar to that of other series. We have not found any significant difference between the age of our patients and the survival, although if we analysed the subgroups, we found that the men equal to or over 50 years of age had a better survival than the women of the same age

Effects of a prostaglandin DP receptor agonist, AL-6598, on aqueous humor dynamics in a nonhuman primate model of glaucoma.

This study examines, in 11 cynomolgus monkeys with unilateral laser-induced glaucoma, the ocular hypotensive mechanism of action of AL-6598, partial agonist at the DP and EP prostanoid receptors. In a crossover fashion, both eyes of each monkey were dosed twice daily with 25 microL of either AL-6598 0.01% or vehicle for 2 days and on the morning of the 3rd day. Measurements were made on day 3 of each treatment. Alternative treatments were separated by at least 2 weeks. Intraocular pressures (IOPs) were measured by pneumatonometry and aqueous flow and outflow facility by fluorophotometry. Uveoscleral outflow was calculated mathematically. In the normotensive eyes, compared to vehicle treatment, AL-6598 decreased IOP from 22.5 +/- 0.7 to 18.7 +/- 0.9 mmHg (P = 0.006), increased uveoscleral outflow from 0.47 +/- 0.17 to 1.22 +/- 0.17 microL/min (P = 0.03), and increased aqueous flow from 1.49 +/- 0.10 to 1.93 +/- 0.13 microL/min (P = 0.01). No measurement in AL-6598-treated hypertensive eyes was significantly different from vehicle treatment. It is concluded that AL-6598 reduces IOP by increasing uveoscleral outflow in normotensive eyes of ketamine-sedated monkeys, despite an increase in aqueous flow. This effect is different from that of PGD(2), which decreases aqueous flow, and of the selective DP receptor agonist, BW245C, which increases both outflow facility and uveoscleral outflow in addition to decreasing aqueous flow.

Characterization of uveoscleral outflow in enucleated porcine eyes perfused under constant pressure.

PURPOSE: A new technique was developed to measure the flow of aqueous humor through the uveoscleral pathway in porcine eyes and to examine whether there is any outflow through the choroid into the vortex veins. METHODS: Enucleated porcine eyes were perfused in vitro under a constant pressure of 10 mm Hg. After total outflow was measured, the episcleral vessels were blocked with cyanoacrylate to eliminate outflow through the conventional pathway. The vortex veins were then blocked, to assess the amount of choroidal drainage. RESULTS: The average outflow in control eyes was found to be 2.8 +/- 0.9 microL/min. After the exit sites of the conventional pathway were blocked, the average outflow decreased to 1.1 +/- 0.5 microL/min. Blocking the vortex veins did not appear to alter uveoscleral outflow further (1.2 +/- 0.8 microL/min). CONCLUSIONS: The results suggest that choroidal drainage into the vortex veins is insignificant in the absence of blood perfusion. No significant washout effects in porcine eyes were observed.

Roles of stem cell factor/c-Kit and effects of Glivec/STI571 in human uveal melanoma cell tumorigenesis.

The B-Raf(V599E)-mediated constitutive activation of ERK1/2 is involved in establishing the transformed phenotype of some uveal melanoma cells (Calipel, A., Lefevre, G., Pouponnot, C., Mouriaux, F., Eychene, A., and Mascarelli, F. (2003) J. Biol. Chem. 278, 42409-42418). We have shown that stem cell factor (SCF) is involved in the proliferation of normal uveal melanocytes and that c-Kit is expressed in 75% of primary uveal melanomas. This suggests that the acquisition of autonomous growth during melanoma progression may involve the SCF/c-Kit axis. We used six human uveal melanoma tumor-derived cell lines and normal uveal melanocytes to characterize the SCF/c-Kit system and to assess its specific role in transformation. We investigated the possible roles of activating mutations in c-KIT, the overexpression of this gene, and ligand-dependent c-Kit overactivation in uveal melanoma cell tumorigenesis. Four cell lines (92.1, SP6.5, Mel270, and TP31) expressed both SCF and c-Kit, and none harbored the c-KIT mutations in exons 9, 11, 13, and 17 that have been shown to induce SCF-independent c-Kit activation. Melanoma cell proliferation was strongly inhibited by small interfering RNA-mediated depletion of c-Kit in these cells, despite the presence of (V599E)B-Raf in SP6.5 and TP31 cells. We characterized the signaling pathways involved in SCF/c-Kit-mediated cell growth and survival in normal and tumoral melanocytes and found that constitutive ERK1/2 activation played a key role in both the SCF/c-Kit autocrine loop and the gain of function of (V599E)B-Raf for melanoma cell proliferation and transformation. We also provide the first evidence that Glivec/STI571, a c-Kit tyrosine kinase inhibitor, could be used to treat uveal melanomas.

The mechanism of action of prostaglandins on uveoscleral outflow.

It is generally accepted that prostaglandins (PGs) lower intraocular pressure by increasing uveoscleral outflow. The growing use of PGs to lower intraocular pressure has led to increased interest in the uveoscleral outflow. Uveoscleral outflow passes through extracellular spaces within the ciliary muscle and then through the suprachoroidal space to the posterior pole of the eye. Recent studies indicate that this reflects a direct effect of PGs on specific ciliary muscle prostanoid receptors. Activation of these receptors stimulates several linked responses, including cAMP formation and induction of c-Fos and c-Jun expression. These signals lead to increased biosynthesis of matrix metalloproteinases, a family of neutral proteinases that can cleave extracellular matrix molecules. These matrix metalloproteinases may initiate the alteration of collagens in the ciliary muscle to increase spaces among ciliary muscle fibers, thereby reducing hydraulic resistance in the uveoscleral outflow pathway.

Aqueous humor dynamics in the aging human eye.

PURPOSE: Healthy subjects were recruited to identify normal, age-associated changes in intraocular pressure and aqueous humor dynamics. METHODS: Normal healthy subjects from two age groups were enrolled in the study: (1) those from 20 to 30 years of age (n = 51) and (2) those 60 years of age and older (n = 53). Intraocular pressure was measured by pneumatonometry, tonographic outflow facility by pneumatonography, and episcleral venous pressure by venomanometry. Aqueous flow and outflow facility were determined by a fluorophotometric technique. Uveoscleral outflow and anterior chamber volume were calculated. Results from the older group were compared with those from the younger group by means of unpaired, two-tailed t tests. RESULTS: Compared with the younger group, the older group showed significant differences as follows: smaller anterior chamber volume (160+/-39 vs. 247+/-39 microl; mean +/- SD; P< .00001), reduced aqueous flow (2.4+/-0.6 vs. 2.8+/-0.8 microl/minute; P = .002), and reduced uveoscleral outflow (1.10+/-0.81 vs. 1.52+/-0.81 microl/minute; P = .009). CONCLUSIONS: In the healthy aging eye, there is a reduction in the production of aqueous humor and a reduction in its drainage through the uveoscleral outflow pathway.

Bunazosin reduces intraocular pressure in rabbits by increasing uveoscleral outflow.

The mechanism of the ocular hypotensive effect of bunazosin hydrochloride (an alpha1-adrenergic antagonist) and the possible intermediary role of prostaglandins were studied in New Zealand albino rabbits. Aqueous flow, outflow facility and uveoscleral outflow were determined by fluorophotometry, and intraocular pressure (IOP) was measured by pneumatonometry on the fourth day of twice daily topical treatment with 0.1% bunazosin. Uveoscleral outflow was measured with a tracer infusion technique at 1 to 2 hours after one dose of 0.1% bunazosin. Total outflow facility was measured by a two-level constant-pressure infusion method before and at one hour after one dose of 0.1% bunazosin. The effect of topically applied cyclooxygenase inhibitors, including 0.25% indomethacin and 0.03% flurbiprofen, on the IOP reduction after bunazosin was evaluated. At 3 hours after the seventh consecutive dose given twice-daily, bunazosin significantly (P<0.001) reduced IOP to 13.4+/-0.8 mm Hg (mean +/- SEM) from a baseline of 19.6+/-1.1 mm Hg. Indomethacin significantly inhibited the IOP reduction after one dose of bunazosin, whereas flurbiprofen did not (repeated measures ANOVA). Bunazosin significantly increased uveoscleral outflow (P<0.05) and total outflow facility (P<0.02), but not fluorophotometric outflow facility or aqueous flow. It is concluded that, in rabbits, 0.1% bunazosin reduces IOP predominantly by increasing uveoscleral outflow. The role of prostaglandins in this effect is equivocal.

Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the pig eye.

Eyes from pigs were studied by corrosion casting technique. Batson's mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the suprachoroidal space. Following polymerisation of the injected mixture the surrounding tissue was dissolved with 10% natrium hydroxide. Macroscopic and scanning electron microscopic findings in casts of the suprachoroidal space are presented. The outer (scleral) surface of the casts was rough, with a fish-scale-like appearance caused by fine lamellas between the sclera and choroid, running from the inner layers of the sclera traversing the space anteriorly to the choroid. Frequently, irregular, Y-shaped branches deriving from the outer surface of the casts were observed. They corresponded to the perivascular space of the vortex veins and represent a possible uveoscleral drainage route for aqueous humour.

Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the human eye.

Human cadaver eyes were studied by corrosion casting technique. Batson's mixture No. 17 (methyl methacrylate) was injected through a sclerotomy into the suprachoroidal space. Following polymerisation of the injected mixture the surrounding tissue was dissolved with 10% natrium hydroxide. Macroscopic and scanning electron microscopic findings in casts of the suprachoroidal space are presented. Due to transscleral drainage of resin from the suprachoroidal space, different types of branches deriving from the outer (scleral) surface of the casts were found. Some of these branches corresponded to the perivascular spaces of both ciliary vessels and vortex veins. In addition, we found branches probably representing channels deriving directly from the suprachoroidal space, communicating with the intrascleral venous plexus. Such channel systems have previously not been described, and their possible relation to the uveoscleral drainage of aqueous humour is discussed.