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Adrenergic drug effects on aqueous outflow facility following ciliary muscle retrodisplacement in the cynomolgus monkey.

Cynomolgus monkeys with untouched, totally iridectomized, or totally iridectomized and ciliary muscle-disinserted eyes underwent two-level constant-pressure perfusion of the anterior chamber to determine the effect of intracameral mock aqueous humor, l-epinephrine bitartrate (10 microgram), l-norepinephrine bitartrate (10 microgram), ergotamine tartrate (1 and 20 microgram), and angiotensin II amide (1 and 100 microgram) on total outflow facility. Ergotamine and angiotensin both tended to decrease facility. Epinephrine and norepinephrine significantly increased facility, approximately 25% and 40%, respectively, beyond the effect of mock aqueous in all three types of eyes. The percentage increases in facility produced by epinephrine and norepinephrine were virtually identical in disinserted and nondisinserted eyes and were independent of starting facility in the individual eyes. Our results prove that the epinephrine- and norepinephrine-induced facility increase in cynomolgus eyes is not mediated by the iris or ciliary muscle and suggest that the increase in total facility is due largely to increased facility across the trabecular meshwork.

Angiotensin Amide↗

Laser therapy and angle-closure glaucoma.

All forms of primary and secondary pupillary block angle-closure glaucoma result in an increased resistance to aqueous flow at the pupil margin. As the pressure in the posterior chamber increases, the iris bows forward until the trabecular meshwork is occluded and aqueous outflow is interrupted. Most pupillary block glaucomas are ocular urgencies and require immediate medical therapy to lower intraocular pressure. The definitive treatment for pupillary block is laser therapy. By creating a hole in the iris, the pressure in the anterior and posterior chambers is equalized, allowing the angle to remain open. This discussion reviews the indications, contraindications, and techniques involved in the laser management of angle-closure glaucomas.

Glaucoma, Angle-Closure↗

MMPs and proteinase inhibitors in the human aqueous humor.

PURPOSE: This study was performed to examine the gelatinolytic and caseinolytic activities and the levels of two proteinase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin) and alpha 2-macroglobulin, in the human aqueous humor. METHODS: Aqueous humor samples were collected during elective surgery in patients with cataracts. Zymography with gelatin- and casein-containing gels was performed. The inhibitors were examined by Western blot analyses, enzyme-linked immunosorbent assay, and dot blot assays. RESULTS: The aqueous humor contained a major band of gelatinolytic activity at a molecular weight of 66 kD and minor bands at 125, 95, and 62 kD. These gelatinases were inhibited by 10 mM ethylenediaminetetraacetic acid (EDTA) or 1,10-phenanthroline. After extended incubation (48 hours), zymography on casein-containing gels showed proteinase bands with molecular weights in the 80- to 84-kD range. Additional bands at 68 and 48 kD also were observed. All the caseinase activities were inhibited by 10 mM phenylmethylsulfonyl fluoride and 1 microgram/ml aprotinin. No inhibition was observed with 5 mM EDTA, 5 microM E-64, or 1 microM pepstatin. These results indicated that the caseinases are serine proteinases. Western blot analysis showed a 53-kD alpha 1-proteinase inhibitor band in the aqueous humor. The concentration was 32.2 +/- 9.9 micrograms/ml, constituting approximately 15% of the total protein. A 360-kD protein band immunoreactive to anti-alpha 2-macroglobulin also was detected. Its level in the aqueous humor was 3.2 +/- 1.3 micrograms/ml. CONCLUSIONS: The gelatinases, serine-like proteinases, and proteinase inhibitors found in the aqueous humor may participate in the remodeling of extracellular matrices in the trabecular meshwork and other tissues bordering the anterior chamber.

Aged↗

Localization of aquaporin CHIP in the human eye: implications in the pathogenesis of glaucoma and other disorders of ocular fluid balance.

PURPOSE: The existence of integral membrane proteins that serve as selective water channels has been postulated to explain the movement of water across plasma membranes. Aquaporin CHIP (channel-forming integral membrane protein of 28 kd) is the first such channel to be characterized and is abundant in human erythrocytes and a variety of secretory and absorptive epithelia of the rat. Because disturbances in the movement of water characterize several ocular diseases, the distribution of CHIP in the human eye was studied. METHODS: Affinity-purified antibodies against purified CHIP protein were used for the indirect immunofluorescence localization of CHIP in human eye structures. Labeling was confirmed by immunoblot analyses of membrane preparations from eye structures. RESULTS: CHIP immunolabeling was found in the corneal endothelium, the lens epithelium, the nonpigmented epithelium of the ciliary process, the iris epithelium, and the endothelium of the trabecular meshwork and the canal of Schlemm. CONCLUSIONS: The presence of CHIP water channels in the secretory and absorptive tissues of the human eye provides a mechanism for transcellular water movement and may be important for understanding diseases of the eye that involve excess or insufficient movement of ocular fluid such as glaucoma, cataracts, and Fuch's dystrophy. In addition, the existence of CHIP in the outflow pathways of the human eye provides a novel explanation for the movement of water out of the eye.

Adolescent↗

[Late postcontusion secondary glaucoma].

The investigation of 33 patients with late postcontusional glaucoma subjected to surgery and followed up for 25 +/- 8.24 months has revealed: the interval accident-surgery is shorter in the close-angle combined forms; the essential mechanisms responsible for glaucoma occurrence are: the alteration of trabecular meshwork (for open-angle glaucoma) and pupillary block (for close angle glaucoma); simple cases required antiglaucoma surgery (trabeculectomy, peripheral iridectomy) and the mixed ones required combined (trabeculectomy, lens extraction, lens implant) or sequential surgeries (antiglaucoma surgery, vitrectomy etc); the glaucomatous process was stopped in 83.4% of the open-angle glaucoma cases and progressed in 23.5% of the close-angle glaucoma cases; the functional improvements post antiglaucoma surgery combined with removal of opacities are lessened by the higher frequency of severe per- and post-operative complication.

Contusions↗

Long-term results of ab externo neodymium:YAG cyclophotocoagulation.

Neodymium: YAG cyclophotocoagulation (CPC) was performed in 128 eyes of 123 patients with refractory glaucoma. In each eye, 40 burns delivered with energy of up to 7 J were placed 1.5 mm behind the limbus in a 360 degrees pattern. The minimal follow-up period was 24 months, with the mean being 36.9 (range, 24-84; SD, 5.8) months. The mean intraocular pressure was 35.0 (range 23-54; SD, 12.2) mmHg preoperatively, 20.6 (range 15-24; SD, 3.5) mmHg after 1 year, and 20.2 (range 12-24; SD, 8.1) mmHg after 2 years. A total of 25 eyes (19.5%) lost 2 or more lines in visual acuity. Success was defined as a lowering of intraocular pressure by > 30% and a decrease in visual acuity of < 2 Snellen lines. By this definition the success rate was 52.4%. There was no correlation with either the diagnosis, the stage of the disease, or the pigmentation of the trabecular meshwork, although patients with secondary traumatic or uveitic glaucoma tended to be less responsive to CPC. The most common acute complication of treatment was transient corneal edema. Phthisis bulbi developed in 1 eye (0.8%). In conclusion, CPC achieved satisfactory long-term control of intraocular pressure in the majority of patients with severe late-stage glaucoma.

Adolescent↗

Limbal microvasculature of the rat eye.

PURPOSE: To define the microvascular anatomy of anterior segment blood supply and aqueous drainage in the rat eye. METHODS: External limbal blood vessels were studied by direct inspection of normal, living rat eyes and eyes injected intracamerally with fluorescein dye. Intraocular connections of these vessels were then documented with scanning electron microscopy of methylmethacrylate microvascular luminal castings. RESULTS: The rat limbus possesses a circumferential vascular ring consisting of a single artery and a venous plexus. The limbal artery communicates with radial anterior ciliary arteries and with perforating arterioles arising from the long posterior ciliary arteries. The venous plexus is connected to a circumferential Schlemm's canal by numerous transcleral, aqueous-containing collector channels and drains into multiple radial veins located within the episclera. CONCLUSIONS: These findings illustrate anatomic similarities between rats and primates, both in anterior segment blood supply and aqueous humor drainage. The rat limbal artery provides collateral perfusion of the anterior segment from anterior and long posterior ciliary systems. The direct communications between identifiable external aqueous-containing veins, a circumferential episcleral venous plexus, and an internal Schlemm's canal provides the anatomic basis for producing chronically elevated intraocular pressure in rats using retrograde injection of mild sclerosing agents into the aqueous humor outflow pathways, and for administering drugs and other agents to the entire trabecular meshwork and Schlemm's canal.

Animals↗

Glaucoma filtration surgery in nonhuman primates using taxol and etoposide in polyanhydride carriers.

PURPOSE: To determine the effect of taxol and etoposide, hydrophobic drugs with antifibrosis activity, on the outcome of filtration surgery in glaucomatous monkeys. METHODS: Elevated intraocular pressure was produced bilaterally in eight cynomolgus monkeys by laser treatment of the trabecular meshwork. Four animals subconjunctivally received a polyanhydride disk containing 1 mg etoposide at the time of posterior lip sclerectomy in one eye; the other eye received an identical disk without drug. Similarly, four animals received a disk containing 50 micrograms of taxol in one eye and a blank disk in the other. RESULTS: Eyes treated with taxol had lower intraocular pressures than control eyes from 20 days after surgery until death. Eyes with satisfactory filtration bleb appearance and patent fistulae on histologic examination had lower intraocular pressures. The intraocular pressure was lower and the duration of success longer in the etoposide-treated eyes (mean, 16 days) compared to that of the fellow eyes (mean, 10 days), but the difference was not statistically significant. CONCLUSIONS: Use of polyanhydride disks containing taxol, but not etoposide, had a marked beneficial effect on intraocular pressure and bleb appearance after experimental filtration surgery in monkeys. The difference between the two agents may result from the greater antiproliferative potency of taxol and its greater duration of release from the polymer.

Animals↗

[Lectin electron histochemistry in the skin in patients with exfoliation syndrome].

Exfoliation syndrome has recently been suggested to have a more widespread distribution from the findings of exfoliative-like material outside the globe. To determine whether exfoliative-like material and exfoliative material are identical, they were characterized by electron microscopic lectin histochemistry using sixteen kinds of lectin; PNA, RCA60 and 120, ABA, DBA, SBA, ConA, LCA, WGA, DSA, PHA-E4 and L4, UEA-I, Lotus, MAM and SSA. The staining pattern indicated that sugar residues in these two materials on the trabecular meshwork, lens, and skin have the same characteristics, containing glycoconjugates with sugar residues of beta-galactosyl, alpha-mannosyl, N-acetyl-D-glucosaminyl, and terminal sialic acid.

Aged↗

Effects of air injection into the corneal stroma of man: an in vitro study.

BACKGROUND: Corneal stromal air injection has been described for assisting the deep dissection of the recipient corneal bed in lamellar grafting. The consistent finding of air entering the anterior chamber is considered an undesirable complication of the procedure. The route of air entry into the anterior chamber has not been investigated previously. METHODS: The route of air passage through the cornea was studied in 10 human cadaver eyes by direct viewing of the inner corneal surface with an operating microscope and by electron microscopy. RESULTS: Air entered the anterior chamber peripheral to Descemet's membrane in every case in the absence of pre-existing corneal pathology. The air expansion of the cornea occurred only along planes occupied by keratocytes and their cell processes and this expansion caused disruption of the keratocytes. CONCLUSIONS: Air injection into the cornea caused bubbles to enter the anterior chamber peripheral to Schwalbe's line, through the trabecular meshwork. The air produced cleavage of the collagen lamellae along those planes occupied by keratocytes and their cell processes since this provides a path of least resistance. Disruption of the keratocytes is a direct mechanical effect. Descemet's membrane and Bowman's layer act as effective barriers to air passage in the normal cornea.

Air↗

Delayed sustained increase in intraocular pressure secondary to the use of polyacrylamide gel (Orcolon) in the anterior chamber.

Orcolon, a new viscoelastic substance, was withdrawn from the market in the United States by the manufacturer (Optical Radiation Corporation [ORC], Azusa, Calif) because of reports of delayed sustained increases in intraocular pressure (IOP) observed in patients who had undergone anterior segment surgery involving the use of this product. We examined the charts of 118 cases of anterior segment surgery involving Orcolon at our institution and found delayed IOP spikes in 20 of the 116 cases that had at least 3 months of follow up. Procedures included cataract extraction, penetrating keratoplasty, secondary intraocular lens implantation, and glaucoma surgery. Response to maximal medical therapy was poor; 11 patients underwent procedures for IOP control, an additional 4 required new or increased medications, and 3 developed persistent iritis, which required steroids. Four patients lost two or more lines of Snellen line chart visual acuity, and one went from counts fingers to light perception. The cause may be related to the presence of small particles of viscoelastic, which could lead to decreased aqueous outflow, particularly in eyes with an already compromised trabecular meshwork.

Acrylic Resins↗

Immunolocalization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 in the anterior segment of the human eye.

PURPOSE: To determine the distribution of transforming growth factor type beta (TGF-beta) in the anterior segment of the human eye. This knowledge is important because TGF-beta may regulate various physiologic responses in the anterior segment by controlling cell proliferation and differentiation, angiogenesis, and extracellular matrix composition. METHODS: Immunohistochemical methods were used to localize the beta 1, beta 2, and beta 3 isoforms of TGF-beta in the anterior segment of the human eye. RESULTS: Eight of eight eyes (six eye bank specimens and two eyes enucleated because of choroidal melanoma) exhibited staining for at least one of the TGF-beta isoforms. TGF-beta 1 was found in superficial limbal epithelial cells (four of eight eyes) and in the stroma proximal to the ciliary processes (seven of eight eyes). TGF-beta 2 was found in superficial limbal epithelial cells (six of eight eyes), the conjunctival stroma (eight of eight eyes), in the ciliary processes (three of eight eyes), and in a diffuse distribution in the region of the radial and circular muscles of the ciliary body (eight of eight eyes). In addition, TGF-beta 2 was found in the stroma adjacent to the pigmented epithelium in the pars plana (eight of eight eyes). TGF-beta 3 was found in white blood cells in one of eight specimens; otherwise it was not found in the anterior segment. The corneal stroma, corneal endothelium, trabecular meshwork, iris, and ciliary epithelia did not exhibit immunoreactivity with the antibodies used in this study. CONCLUSION: TGF-beta 1 and TGF-beta 2 have a distinct and specific distribution in the anterior segment of the adult human eye.

Adult↗

Melanocytoma of the ciliary body with scleral extension.

A 35-year-old woman had a circumscribed pigmented scleral lesion overlying a pigmented mass in the ciliary body and trabecular meshwork. Sclerectomy and iridocyclectomy were performed. Histologically, the lesion proved to be a melanocytoma. This represents to our knowledge the fourth reported case of scleral extension of a ciliary body melanocytoma.

Adult↗

Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis.

PURPOSE: To investigate increased free radical activity and the accumulation and localization of lipid peroxidation in the anterior segment of the eye with uveitis. METHODS: Experimental autoimmune uveitis (EAU) was induced in rats using human S-antigen peptide. Conjugated dienes (CD) and keto-dienes (KD) were then extracted from the cornea, iris-ciliary body and lens of the EAU eyes. The quantity of CD and KD were determined by measuring ultraviolet absorption and estimating by means of a molar extinction coefficient. Frozen sections of EAU eyes were reacted with 3-hydroxy-2-naphthoic acid hydrazide (NAH), and NAH-carbonyl compounds were detected using a confocal laser scanning microscope. Statistical comparisons of CD and KD products between the EAU groups and controls were performed using the Student's t-test. RESULTS: Compared to controls, CD and KD were significantly increased in the cornea and iris-ciliary body of EAU eyes. Lenses of EAU eyes showed a tendency to elevated levels of CD and KD. In EAU, primarily the anterior border layer and the posterior epithelium of the iris--and, to a lesser extent, the trabecular meshwork and corneal endothelium--revealed positive fluorescence staining for peroxidized carbonyl products. No staining was observed on the ciliary epithelium. CONCLUSIONS: Free radicals and lipid peroxidation products are generated in the anterior segment of the eye in EAU. Because the individual tissues in the anterior segment are composed of various levels of fatty acids and different concentrations of antioxidants, the extent of tissue damage from lipid peroxidation may represent a balance between the fatty acid composition and the antioxidant distribution in each of the tissues.

Amino Acid Sequence↗

Histologic observations of bone remodeling adjacent to endosteal dental implants.

To examine bone morphology associated with endosteal dental implants at various time intervals, we inserted 20 one-stage and 20 two-stage titanium blade implants and 20 one-stage and 20 two-stage titanium root-form implants into 30 dog mandibles. Sixteen implants in 6 control (c) dogs (in situ five months) did not receive bridgework. Sixty-four implants in 24 dogs supported bridges for six, 12, 18, or 24 months. The entire area of the mandible containing the implants was examined by routine light and Nomarski differential interference microscopy (NM) for bone morphology (including osteon orientation) at the implant surface and at regions away from the implant. Control root-form implants were apposed by woven bone, with homogenous compact bone in the cortical plate distant to the implant. After 6 mo of load, immature bone was predominant apposing the implant, but initial osteonal maturation was apparent. NM clearly demonstrated the interstitial and concentric lamellae of the bone. Surprisingly, compact bone formed internal to the cortical plate, an area where trabecular bone is expected. At later periods of load, more mature osteons were seen apposing the implants; however remodeling events were still apparent. These remodeling events extend further away from the implant than was expected if the events resulted only from surgical repair. Also, when the implant inclined so that half was totally in the cortical plate and half in the marrow (in trabecular patterns), osteonal bone appeared to remodel in both areas. Control blade implants and blades loaded for six months were apposed by immature osteons when the implant was placed into the cortical plate. A trabecular meshwork was inferior to the osteonal bone. At 12 mo of load, the bone internal to the cortical plate appeared similar to the lamina dura supporting teeth; however, no PDL existed; the lamina-dura-like pattern directly apposed the implant. Even after 24 mo of load, extensive bone remodeling was apparent adjacent to the implant, markedly different from the bone making up the existing cortical plate. From these data, remodeling activities to blade implants may involve the development of a lamina-dura-like bone morphology after longer periods of load. Osteonal bone was apparent, but only at regions where the implant was inserted into the cortical plate. Further, bone remodeling was apparent even after long periods of load.

Alveolar Process↗

Comparison of the configuration of the human anterior chamber angle, as determined by the Spaeth gonioscopic grading system and ultrasound biomicroscopy.

PURPOSE: The primary purpose of this investigation was to validate anatomically, if possible, the Spaeth gonioscopic grading system. METHODS: The gonioscopic appearance of the anterior chamber angle of 22 patients was described, using a Zeiss 4-mirror gonioscopic lens; the angle was graded according to the Spaeth gonioscopic grading system (SGGS) previously described elsewhere. This system provides a more comprehensive characterization of the angle than other methods, including the site of iris insertion, the angular approach to the recess and the curvature of the peripheral iris. The same patients were then evaluated with biomicroscopic ultrasound examination of the anterior segment; the nature of the anterior chamber angle was described independently by two observers. The two methods of characterizing the anterior chamber angle were then compared. RESULTS: There was a high correlation between the two different methods of characterizing the anterior chamber angle. Ultrasound biomicroscopy had limitations relating to inability to distinguish between iris-cornea apposition and iris-cornea adhesion, and to exact location of the posterior trabecular meshwork. The angularity of the approach to the anterior chamber angle using the SGGS tended to be underestimated by about 5 degrees. Other aspects showed high correlation. CONCLUSION: The SGGS appears to be an accurate method of characterizing the anatomic appearance of the anterior chamber angle in patients. It also provides a more comprehensive description of the angle that other grading systems.

Anterior Chamber↗

[Treatment with silicone oil in complicated retinal detachment. Anatomopathological test of 2 enucleated eyes].

Two eyes with a complicated retinal detachment were operated using intraocular silicone oil injection. They were enucleated 33 and 12 months after the operation because of painful secondary glaucoma and corneal dystrophy. Using light and electron microscopy, silicone oil vacuoles were observed in the corneal depth, the iris stroma, the trabecular meshwork and in lens remnants. There was an angle closure due to iridocorneal synechia. The same vacuoles were recognized in epiretinal membranes, in the internal and external layers of the retina and in the pigment epithelium. When the retina was detached, silicone oil vacuoles were present in the choroidal vessels.

Aged↗

Prophylactic Nd:YAG-laser iridotomy versus surgical iridectomy: a randomized, prospective study.

Both surgical iridectomy and YAG-laser iridotomy have been shown to prevent angle-closure glaucoma. However, it remains unknown as to which procedure is superior. We therefore conducted a prospective randomized study, which compared the effect of the two methods on visual acuity, intraocular pressure, endothelial cell density, depth of the anterior chamber, and iris configuration as well as acceptance by the patients. A total of 30 patients, who were treated for acute angle-closure glaucoma in one eye, were subjected to either surgical iridectomy or Nd:YAG-laser iridotomy in the other eye according to a randomized protocol. All patients were followed for 12 months by examination at the 1st, 6th, and 12th month post treatment. No significant difference between the two treatments was found regarding visual acuity or intraocular pressure. The peripheral anterior chamber increased in depth following both methods, whereas the central depth of the anterior chamber was unaffected. A better gonioscopic visibility of the trabecular meshwork resulted from the increased width of the chamber angle. Whereas the number of endothelial cells remained constant in the patients treated with laser iridotomy, a small decrease was observed in the group of patients who underwent iridectomy (-7.2% after 12 months; difference not significant). The subjective acceptance by the patients was better in the group treated with laser iridotomy. We conclude that the two methods are equivalent with regard to intraocular pressure and visual acuity. The constant number of endothelial cells and the better acceptance by the patients suggest Nd:YAG-laser iridotomy to be the preferable method for prophylaxis of acute angle-closure glaucoma.

Acute Disease↗