Sites of breakdown of the blood-aqueous barrier after paracentesis of the rhesus monkey eye.

Sites of breakdown of the blood-aqueous barrier following rapid paracentesis have been investigated in rhesus monkeys with two independent procedures. (1) The entrance of fluorescein into the anterior and posterior chambers following paracentesis was studied in vivo in normal eyes, in eyes with laser-induced experimental glaucoma, and in totally iridectomized eyes. (2) Scanning electron microscopy was used to study the ciliary body and trabecular meshwork regions in normal eyes and paracentetic eyes. These investigations show that the ciliary body, particularly the anterior pars plicata region, is a source of secondary aqueous humor protein. In addition, the study shows reflux of blood into Schlemm's canal and plasma movement across the inner wall into the anterior chamber.     

The HNK-1 epitope in the inner connective tissue layer of the human ciliary body in exfoliation syndrome and various types of glaucoma

Possible changes in the expression of the HNK-1 carbohydrate epitope in the inner connective tissue layer of the human ciliary body, located between the ciliary epithelium and muscle, was studied using 2 formalin-fixed, paraffin-embedded eyes with exfoliation syndrome, 33 eyes with different types of glaucoma, and 21 morphologically normal control eyes. A strong immunoreaction delineating cell processes was observed in this layer with monoclonal antibodies HNK-1 and VC1.1 recognizing the HNK-1 epitope in control specimens, whereas partly granular immunoreaction was present in eyes with exfoliation syndrome. Exfoliation material was also immunoreactive. In all types of advanced glaucoma, the immunoreaction was mostly granular in nature and greatly diminished. No difference in HNK-1 immunoreactivity between control and glaucoma eyes was seen in the retina and ciliary epithelium. Elevated intraocular pressure, either directly or by decreasing blood flow to the ciliary body, may cause degenerative or metabolic changes in the inner connective tissue layer cells that bear or secrete molecules sharing the HNK-1 epitope. The partly granular immunoreactivity in eyes with exfoliation syndrome only indicates changes in this epitope even without an increase in intraocular pressure.     

Immunomicroscopical study of type VI collagen in the trabecular meshwork of normal and glaucomatous eyes

Cross-strained fiber bundles called long-spacing collagen or curly collagen occur in normal eyes in the trabecular meshwork. It can be seen in the basement membrane of the trabecular lamellae, in the sheath of the elastic-like fibers and underneath the inner wall of Schlemm's canal, where it forms part of the so called plaque material. The amount of this long-spacing collagen increases with age and is significantly more pronounced in glaucomatous eyes. Using immunohistochemical and immuno-electronmicroscopic methods, we have been able to show that type VI collagen is present in the aggregates called long-spacing collagen.     

Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys

PURPOSE: To determine in rhesus monkeys the age-dependence of uveoscleral outflow (Fu) and morphology of the trabecular meshwork (TM) and anterior ciliary muscle (CM). METHODS: Intraocular pressure (IOP) was measured by Goldmann applanation tonometry in monkeys under ketamine anesthesia. After anterior chamber cannulation under pentobarbital anesthesia, aqueous humor formation (AHF), anterior chamber volume, trabecular outflow, and Fu were determined isotopically. The CM and TM were examined by light and electron microscopy. RESULTS: IOP increased significantly with age in monkeys aged 3 to 29 years. AHF and anterior chamber volume were unchanged. Fu was decreased, and trabecular outflow increased in monkeys aged 25 to 29 years compared with the remaining monkeys. Morphologically, there was a significant increase in the thickness of the elastic fibers of the trabeculum ciliare covering the anterior tips of the CM, and an increase in extracellular material between the muscle tips. The number of TM cells decreased with age, whereas the amount of fibrillar material and sheath-derived plaques increased. This increase was less pronounced in the middle filtering portion of the cribriform region than in the anterior and posterior portions. CONCLUSIONS: The decline in Fu in very old rhesus monkeys with normal IOP parallels that seen in normotensive aging humans. This may be correlated with thickening of the elastic fiber sheath in the CM tips in addition to other morphologic changes. The TM findings are analogous to those in the aging human eye and are consistent with the age-related decrease in outflow facility reported in both humans and monkeys.     

Uveal damage in secondary glaucoma

In a morphometric study, we investigated histopathologic changes in the ciliary body and retinal pigment epithelium in eyes with secondary glaucoma. Eyes with malignant melanoma served as controls. The mean thicknesses of the ciliary muscle and inner connective-tissue layer of the pars plicata were significantly lower (P < 0.001) in glaucomatous than in melanomatous eyes, as was the mean width of the stromata of ciliary processes (P < 0.001). With increasing age, the ciliary muscle in melanomatous eyes became significantly thinner (P < 0.001). The width of the stroma at the base of the ciliary process was significantly correlated with the thickness of the inner connective-tissue layer of the pars plicata in both groups of eyes (P < 0.001). The mean number of ciliary processes was significantly lower in glaucomatous than in melanomatous eyes (P < 0.001), as was the mean height of pigment epithelial cells in the midperipheral retinaP < 0.05). The present study revealed quantitative glaucomatous tissue changes in the ciliary body and retinal pigment epithelium.     

Structural changes of the trabecular meshwork in different kinds of glaucoma

The morphology of the trabecular meshwork in three types of open angle glaucoma: primary open angle glaucoma (POAG), corticosteroid-induced glaucoma and pigmentary glaucoma (PG) are described.Ageing is one major risk factor for development of POAG. It is assumed that preexisting age-related changes of the trabecular meshwork (TM) play a role for the development of increased outflow resistance and intraocular pressure (IOP) in various types of glaucoma. These age-related changes in the TM develop concomitant with that of presbyopia. Therefore the functional relationship between ciliary muscle (CM) and TM and the age-related changes in morphology of the outflow system are described first. One main finding in the ageing TM concerns changes of the elastic fiber network and the anterior elastic tendons of the CM. There is an increase in thickness of the sheath of the elastic fibers. Cross-sections through these fibers with their sheath appear as extracellular plaques and were therefore termed “sheath derived plaques” (SD-plaques).Morphologically, the TM changes in POAG resemble that of the ageing TM, but in POAG there is a significant increase in SD-plaques compared to age-matched controls. This increase is due to fine fibrils and other components of the extracellular matrix (ECM) that adhere to the sheaths of the elastic fibers and their connections to the inner wall endothelium. In POAG eyes there is also a marked loss of TM cells, at places leading to fusion and thickening of trabecular lamellae.In steroid-induced glaucoma there is also an increase in fine fibrillar material in the subendothelial region of SC. In contrast to POAG eyes these fibrils do not adhere to the sheath of the elastic fibers but are deposited underneath the inner wall endothelium. The main finding in steroid-induced glaucoma is an accumulation of basement membrane-like material staining for type IV collagen. These accumulations are found throughout all layers of the TM.In pigmentary glaucoma loss of cells was more prominent than in POAG eyes. Presumably, this cell loss occurs after overload of TM cells with pigment granules. Denuded TM lamellae fuse and the TM collapses. In the subendothelial region of these collapsed TM areas an increase in ECM presumably due to underperfusion was observed. At other places SC was occluded and the cribriform region appeared disorganized. In most parts of the circumference of the eye, the TM cells contained pigment granules. Occlusion of TM spaces by pigment granules or cells loaden with pigment was not seen in eyes with PG.     

Hyaluronan synthase immunoreactivity in the anterior segment of the primate eye

The anterior segment of human and cynomologus monkey eyes was investigated for the presence of hyaluronan (HA) synthesizing cells using a polyclonal antibody against the enzyme HA synthase (HAS). In the chamber angle region the most intense staining was seen in the cell membranes of the corneal endothelium and in monkey eyes in the cells covering the posterior extension of the cornea (the operculum). The trabecular meshwork cells of the uveal and inner corneoscleral lamellae were also intensely stained. On the other hand, no staining was observed in the trabecular cells of the outer corneoscleral and the cribriform meshwork. The cell membranes of the inner wall endothelium of Schlemm's canal were labelled only at their luminal surface.In the iris stroma and the trabeculum ciliare (the ciliary body band), labelled cells were also found, whereas the connective tissue of the ciliary muscle and the muscle itself did not contain HAS-positive cells. In the ciliary processes immunoreactivity was seen in the non-pigmented epithelial cells (NPE) covering the anterior tips of the processes, suggesting that HA found in the aqueous humor is produced by these cells. The pars plana NPE showed the most intense staining in the cells directly adjacent to the ora serrata region. The hyalocytes found in the neighborhood of the pars plana also showed intense HAS immunoreactivity. It is likely that both hyalocytes and NPE cells of the posterior pars plana release HA into the vitreous.The study was supported by grants from Deutsche Forschungsgemeinschaft, Bonn, Bad Godesberg (Dr 124/6-1)     

睫状环阻滞性青光眼的超声生物显微镜检查

目的 应用超声生物显微镜结合Ａ超检查睫状环阻滞性青光眼,以了解急性发作时睫状环阻滞的状况。方法 对２７例（３１只眼）抗青光眼术后发生的睫状环阻滞性青光眼进行实时超声生物显微镜检查,与同一眼术前的超声生物显微镜影像进行对比观察;并以５４只正常眼和７２只原发性闭角型青光眼作为对照研究。结果 睫状环阻滞性青光眼发作时,１８只眼（５８．１％）睫状体和晶体完全相贴,１３只眼（４１．９％）睫状体和晶体间有一间     

Clusterin deficiency in eyes with pseudoexfoliation syndrome may be implicated in the aggregation and deposition of pseudoexfoliative material

PURPOSE: To determine the role of the extracellular chaperone clusterin in the pathophysiology of pseudoexfoliation (PEX) syndrome/glaucoma, which is characterized by the stable deposition of abnormal extracellular fibrillar material in anterior segment tissues. METHODS: Real-time PCR, in situ hybridization, and immunohistochemistry were applied to analyze the mRNA and protein expression of clusterin in PEX eyes of patients without and with glaucoma and to compare them with eyes of patients with primary open-angle glaucoma and angle-closure glaucoma and with normal control eyes. Aqueous levels of clusterin were determined by Western blot analysis. Real-time PCR and Western blot analysis were used to study the effect of TGF-beta1, which is significantly increased in the aqueous humor of PEX eyes, on clusterin expression by nonpigmented ciliary epithelial cells in vitro. RESULTS: Clusterin mRNA was ubiquitously expressed in most ocular cells and tissues, particularly in the epithelium of ciliary processes, whereas the protein was mostly located to extracellular structures, such as ocular basement membranes and stromal fibers. Real-time PCR and in situ hybridization displayed significant downregulation of clusterin mRNA in all anterior segment tissues of PEX eyes, irrespective of the presence or type of glaucoma, compared with normal and glaucomatous control eyes, whereas posterior segment tissues did not show any differential expression. A generally decreased immunoreactivity, but a prominent binding of clusterin to all PEX deposits, could be observed in ocular tissues of PEX eyes. Clusterin levels in aqueous humor were significantly reduced in eyes of patients with PEX syndrome compared with normal and glaucomatous control eyes. The expression of clusterin mRNA and protein in nonpigmented ciliary epithelial cells was significantly downregulated by TGF-beta1 in vitro. CONCLUSIONS: Considering the known role of clusterin as a highly efficient extracellular chaperone, its deficiency in the anterior segment of PEX eyes may promote the stress-induced aggregation and stable deposition of the pathologic extracellular matrix product characteristic of PEX syndrome.     

恶性青光眼发病机制及临床分型的研究

目的 研究恶性青光眼的发病机制,为它的临床分类提供依据。方法 采用眼科超声生物显微镜、眼科Ａ,Ｂ型超声以及眼科临床检查方法及诊断性手术对１２例恶性青光眼病例进行了活体眼部解剖结构的定性及定量观察,并采用对照研究的方法和对侧眼进行了比较研究,按照观察结果结合临床表现对恶性青光眼的分类提出了新的建议。结果 在１２例病例中有４例（３３．３％）经超声生物是微镜证实存有睫状环阻滞的特征,且对侧眼存在眼前段侠     

睫状环阻塞青光眼的综合治疗

目的 探讨睫状环阻塞性青光眼综合治疗的效果.方法 16例（19眼）睫状环阻塞性青光眼,7例（8眼）进行散瞳、皮质类固醇、降眼压等药物治疗,9例（11眼）进行品状体超声乳化、前段玻璃体切除、后囊环形撕开及人工晶状体植入术.结果 4例（5眼）经药物治疗前房恢复正常、眼压正常,12例（14眼）多联手术后均获得正常前房深度和眼压.结论 睫状环阻塞性青光眼是多机制混合存在的难治性青光眼,需采用药物及多联手术相结合的治疗方法.     

Light and electron microscopy of the anterior chamber angle structures following surgical disinsertion of the ciliary muscle in the cynomolgus monkey.

Light and electron microscopic studies were done on 11 cynomolgus monkey eyes which had undergone total iris removal followed by surgical disinsertion of the ciliary muscle from the scleral spur 4.7 to 14.4 months earlier. Anterior chamber perfusion to measure gross outflow facility had been performed one to nine times postoperatively. Over most of the circumference in most eyes (1) the ciliary muscle had been retrodisplaced from the scleral spur and had reattached to the sclera more posteriorly; (2) ciliary muscle, trabecular meshwork, and Schlemm's canal appeared normal. A cyclodialysis cleft was never seen. Fixation of some eyes in the in vivo and in vitro presence of pilocarpine demonstrated the contractibility of the retrodisplaced muscle. In isolated areas where the ciliary body had been surgically cut, scar tissue of varying thickness connected scleral spur, sclera, ciliary body, zonule, and lens capsule, but did not infiltrate trabecular meshwork or Schlemm's canal. In such sectors, plasma cell-like cells replaced trabecular endothelial cells and were also present in the scar tissue, ciliary muscle, and surrounding vessel walls in the scar and sclera. In sectors of two eyes, a previously existing trabecular operculum extended posteriorly and completely covered the meshwork. The meshwork in these sectors was poorly perfused by aqueous humor, and electron-dense deposits were present beneath the inner wall of Schlemm's canal. Four totally iridectomized and two unoperated eyes from these monkeys were also examined; ciliary muscle, trabecular meshwork, and Schlemm's canal appeared normal in all, despite the numerous anterior chamber perfusions.     

原发性先天性青光眼眼前段活体结构观察

目的:观察先天性青光眼的超声生物显微镜(UBM)图像特征并探讨先天性青光眼的发病机制。方法:采用高频、高分辨率的超声生物显微镜对6例先天性青光眼患者10只眼的房角、虹膜、睫状体等进行扫描和分析,并与7例正常人或无相关疾病患者的7只眼进行比较。结果:超声生物显微镜检查显示出原发性先天性青光眼的房角、虹膜、睫状体及巩膜突发育不良,虹膜基质薄,睫状体细小,巩膜突解剖特征不明显。原发性先天性青光眼组的虹膜厚度及睫状体大小的测量和统计学比较均明显小于正常对照组。结论:超声生物显微镜可以观察到常规眼科检查观察不到的部位,如睫状体、房角隐窝、虹膜后表面等等。原发性先天性青光眼具有虹膜基质薄、睫状体细小、巩膜突解剖特征不明显等特征,提示原发性先天性青光眼除了房角发育异常外,尚合并存在虹膜、睫状体巩膜突发育不良。其中虹膜、睫状体发育不良可能是先天性青光眼相对比较重要的发病机制。眼科学报1998;14:83—86。     

青光眼术前睫状体脱离的超声生物显微镜观察

目的：应用超声生物显微镜对急性闭角型青光眼术前睫状体脱离的组织结构进行形态学检查,方法：对青光眼病入术前常规进行超声生物显微镜检查,发现有睫状体脱离。对睫状体脱离者与非睫状体脱离者按年龄、性别、眼压降低幅度,眼前节解剖结构的测量数据进行统计学处理。结果：术前睫状体脱离多出现于眼压50mmHg以上,迅速降至正常或更低,房角大部分关闭但未完全关闭的病人,在272眼急性闭角型青光眼中发现有睫状体脱离者37眼占13．6％,与病人年龄、性别、眼前节解剖参数无显著性的差异,结论：术前睫状体脱离与眼压迅速下降有关。     

Echothiophate-induced structural alterations in the anterior chamber angle of the cynomolgus monkey.

Four cynomolgus monkeys were treated topically twice daily in one eye with echothiophate iodide (PI) doses of 63, 75, or 250 micrograms per treatment for 7.7 weeks to 7 months. The opposite eyes of two monkeys received a control solution (diluent). The anterior ocular segments of all six eyes were studied by light and transmission electron microscopy during treatment. In the PI-treated eyes, the cribriform and outer corneoscleral meshwork were unusually dense. The trabecular meshwork was collapsed and the lamellae showed thickened basement membranes and thickened sheaths of elastic-like material. Most endothelial cells were enlarged and activated. Some contained many glycogen particles; others showed evidence of degeneration. The cribriform meshwork contained much more extracellular fine fibrillar material than normal, and the endothelium of the inner wall of Schlemm's canal was damaged. The PI-contracted ciliary muscle had a more rectangular shape than normally contracted muscles, and the inner edge extended so far anteriorly that in some areas it overlapped and occluded the trabecular meshwork. The muscle cells appeared damaged, and their basement membranes were thickened. The nonpigmented epithelial cells of the ciliary processes showed signs of degeneration, and within the pars plana some contained large, weakly osmiophilic inclusions. The basement membrane of the ciliary epithelium was thickened everywhere. The stromal vessels of the pars plana were dilated, and signs of inflammation were present. The sphincter iridis was damaged and there were iridocorneal adhesions. The 5 month diluent-treated eye demonstrated mild structural abnormalities in the meshwork.     

前部视网膜、睫状体冷凝联合复合式小梁切除术治疗新生血管性青光眼的临床研究

目的探讨前部视网膜、睫状体冷凝联合复合式小梁切除术治疗新生血管性青光眼的临床疗效。方法 2007年2月至2011年3月我院共收治新生血管性青光眼患者32例(32眼),均采用前部视网膜、睫状体冷凝联合复合式小梁切除术治疗,术后随访6～12个月,观察患者术后一般疗效、视力、眼压及并发症等情况。结果 32眼中手术完全成功28眼,条件成功2眼,失败2眼,手术成功率为93.8%。术后25眼视力有所提高,2眼丧失视力,其余患者保持术前视力,未有明显变化。28眼眼压在正常范围内波动;2眼眼压在术后3个月、4个月时升高,给予抗青光眼药物治疗后眼压得以控制;2眼眼压高于30mmHg(1kPa=7.5mmHg),二次手术后控制在正常范围内。术后并发症主要有前房积血、浅前房、前部葡萄膜炎、玻璃体出血等。结论前部视网膜、睫状体冷凝联合复合式小梁切除术治疗新生血管性青光眼,术后疗效确切,并发症少。     

Ultrasound biomicroscopic imaging demonstrate thinner ciliary body thickness in eyes with angle closure

AIM: To compare the ciliary body thickness between eyes with primary angle closure (PAC) and primary angle-closure glaucoma (PACG) with the normal eyes, and to investigate the association between ciliary body thickness and ciliary processes situation. METHODS: In this cross-sectional study, 57 patients with PAC/PACG were matched to 57 normal subjects after propensity score matching (PSM) adjusting for age and gender. All subjects underwent conventional ocular examinations and ultrasound biomicroscopy (UBM) examination, among which the patients with PAC/PACG performed the examinations one month after laser peripheral iridotomy (LPI). Quantitative parameters were measured, which included ciliary body thickness at the position of 1 mm posterior to the scleral spur (CBT1), trabecular-ciliary process distance (TCPD) and trabecular-ciliary process angle (TCA). RESULTS: Eyes with PAC/PACG presented significantly thinner CBT1, shorter TCPD and smaller TCA (P<0.001) than the normal eyes, both in comparison of the means of four quadrants and in comparisons of each quadrant. After removing images with peripheral anterior synechia (PAS), the same results were also found in comparisons between the two groups. Significant correlations were found between TCPD (R2=0.537, P<0.001) and TCA (R2=0.517, P<0.001) with CBT1. CONCLUSION: Eyes with PAC/PACG have thinner ciliary body thickness and more anteriorly situated ciliary processes. Thinner ciliary body thickness is associated with anterior situation of the ciliary processes.     

Neovascular glaucoma and carotid artery obstructive disease

Carotid artery obstructive disease, although infrequently diagnosed as a primary or contributing cause of neovascular glaucoma, can produce distinctive characteristics. Decreased perfusion of the ciliary body may decrease aqueous humor production. As a result, such eyes with neovascular glaucoma may occasionally be normotensive or even hypotensive. Fluorescein angiography may show an increased arm-to-retina time and leakage from the major retinal arterioles. Panretinal photocoagulation may not eliminate the anterior segment neovascularization because of anterior segment ischemia. Endarterectomy can significantly increase intraocular pressure as perfusion to the ciliary body returns to normal. These characteristics were found in two patients, a 67-year-old woman and a 49-year-old man, with diabetes and hypertension. In both cases cyclocryotherapy significantly reduced the intraocular pressure and the rubeosis iridis regressed.     

Histometrische Untersuchungen über die Kammerwinkelregion des menschlichen Auges bei verschiedenen Altersstufen und Glaukomformen

Zusammenfassung An 30 menschlichen Augen aller Altersstufen sowie an insgesamt 47 Augen verschiedener Glaukomformen wurden die proportionalen Verhältnisse der Kammerwinkelregion morphometrisch am Sagittalschnitt bestimmt. Es ergab sich, daß der Durchmesser des Schlemmschen Kanals sowie die Distanz zwischen Scleralsporn und Descemet nach der Geburt zunehmen, vom 5. Lebensjahr an jedoch konstant bleiben. Auch der Scleralsporn verlängert sich noch merklich in den ersten Lebensjahren, wobei sich die vordere Ciliarmuskelspitze nach vorn verlängert. Die Ausdehnung des Schlemmschen Kanals nach vorn erfolgt wahrscheinlich in einem präformierten Gewebsbereich zwischen Scleralseptum und prospektiver Innenwand, deren äquatorial verlaufendes, straff geordnetes Gitterfasergerüst bereits beim Neugeborenen differenziert ist.Die Proportionsverhältnisse der Kammerwinkelregion stimmten bei normalen Erwachsenen (5.–86. Lebensjahr), bei sekundären und primärchronischen Glaukomen weitgehend überein. Abweichungen fanden sich beim Glaucoma chronicum congestivum (Engwinkelglaukom). Hier war vor allem die Distanz zwischen dem hinteren Ende der Descemetschen Membran und dem des Schlemmschen Kanals verlängert; Scleralsporn und vordere Ciliarmuskelspitze ragten weiter nach vorn über das Ende des Kanals hinaus als beim Vergleichsmaterial der übrigen Gruppen. Über die Form und Tiefe der Kammerbucht kann auf Grund des vorliegenden Materials nichts ausgesagt werden.Es wird in Übereinstimmung mit den Befunden neuerer klinischer und echographischer Befunde angenommen, daß sich das zum Anfallsglaukom disponierte Auge in seinen Proportionen vom Normalen und Simplexglaukomauge unterscheidet.

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Histometric studies on the chamber angle area in human eyes of various groups of age and glaucoma

Summary The proportional relationships in the chamber angle region were determined morphometrically in sagittal sections of 30 human eyes of all age groups and of a total of 47 eyes with various forms of glaucoma. It was shown that the diameter of Schlemm's canal and the distance between the scleral spur and Descemet's membrane increase after birth but remain constant beginning from the age of 5 years. The scleral spur is also lengthened noticeably during the first years of life and the anterior tip of the ciliary muscle is lengthened frontally. Schlemm's canal extends itself toward the front probably in a pre-formed tissue area between the scleral septum and the prospective inner wall of the canal whose equatorially arranged lattice framework of tensely interwoven reticulin fibers is already differentiated in the new-born.The proportional relationships in the chamber angle area of normal adults (aged 5–86 years) coincide very nearly with those in cases of secondary und primary chronic glaucoma. Divergencies were found in cases of glaucoma chronicum congestivum. Here, the distance between the posterior extremity of Descemet's membrane and that of Schlemm's canal is increased and the scleral spur and the anterior tip of the ciliary muscle project farther forward beyond the end of the canal than in the comparison material of the other groups (cf. table). The material did not allow a statement as to form and depth of the chamber angle itself.In agreement with more recent clinical and echographic findings it is presumed that the proportions of an eye which is pre-disposed to a glaucoma chronicum congestivum differ from those of normal and simplex glaucomatous eyes.

     

Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide

PURPOSE. To investigate long-term changes in the anterior segment of primate eyes treated for one year with different prostaglandin agonists and a prostamide. The results were compared with those obtained after vehicle treatment and in untreated controls. METHODS. Sixteen young cynomolgus monkeys were unilaterally topically treated for 1 year with either bimatoprost 0.03% (prostamide), sulprostone 0.03% (EP(3)/EP(1) agonist), AH13205 0.1% (EP(2) agonist), or latanoprost 0.005% (FP agonist), which all lower IOP in this species at the doses applied. Four animals were treated with the vehicle only. In all cases the left eye was treated, the right eye remained untreated. Six monkeys served as untreated controls. Sections from 4 quadrants each of the circumference of the eyes of 16 drug-treated, 4 vehicle-treated and 6 untreated control animals were investigated qualitatively and quantitatively using light- and electronmicroscopy. The area of widened spaces between ciliary muscle bundles, the number of nerve fiber bundles at the muscle tips, and the width and length of the ciliary muscle were quantitated. RESULTS. The general morphology of the ciliary muscle and trabecular meshwork was normal in appearance and shape in all animals, whereas some localized morphologic changes were observed in the drug-treated animals. The changes were found to be similar in all four treatment groups. In the ciliary muscle, there was a significant increase in optically empty spaces between muscle bundles in the anterior portion of the longitudinal and the reticular ciliary muscle compared with untreated and vehicle-treated control animals. Within these spaces, significantly more myelinated nerve fiber bundles were found in drug-treated compared with normal control animals. Ultrastructurally the spaces were partly covered by endothelial-like cells which, in some areas, were in contact with the basement membrane of the microvasculature. In all treatment groups, there were also changes in the trabecular meshwork region. Significant regional differences among the different quadrants of the eyes and quantitative differences between treatment groups were observed. The ciliary epithelium had a normal appearance in all treatment groups. CONCLUSIONS. After one year of treatment with different prostaglandins and a prostamide, uveoscleral outflow pathways are enlarged and appear organized. Conventional outflow routes were also affected. Long-term treatment with AH13205, latanoprost, sulprostone, or bimatoprost also induces sprouting of nerve fibers.