持续性低眼压对视网膜影响的实验研究

目的　探讨持续性低眼压对视网膜结构和功能的影响。方法　青紫兰兔 48只 ,随机分为 6组。实验组动物双眼均接受CO2 激光外路巩膜切除术。术后每日测量眼压 ,观察兔视网膜的组织形态学变化及视觉功能的改变。统计学分析采用单因素方差分析、q检验和q′检验。结果　光学显微镜及透射电子显微镜下可见 :随着低眼压持续时间的延长 ,视网膜各层次第发生改变 ,低眼压持续时间愈长 ,病变愈明显。VEP和ERG检测结果显示 :低眼压组P2 波、a波及b波振幅下降、时值延长 ,与正常组相比差异具有显著性意义 (P <0 0 5 )。结论　持续性低眼压能造成视网膜的结构损伤和功能下降。     

Management of traumatic cyclodialysis cleft associated with ocular hypotony.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of direct cyclopexy for treatment of traumatic cyclodialysis cleft associated with ocular hypotony. PATIENTS AND METHODS: Eyes with traumatic cyclodialysis cleft were treated with direct cyclopexy or 1.0% atropine eyedrop. RESULTS: Five eyes with a large cyclodialysis cleft were treated with direct cyclopexy. Postoperatively, these eyes obtained normal intraocular pressure. Four of the 5 eyes had good visual acuity, and 1 eye that had preoperative subretinal hemorrhage in the macula had poor visual acuity. Of the 3 eyes treated with 1.0% atropine eyedrops, 1 had good visual acuity, and 2 with retinal folds had fairly good and poor visual acuity. CONCLUSION: The present study showed that direct cyclopexy is useful for the treatment of traumatic cyclodialysis cleft associated with ocular hypotony, and that the cyclodialysis should be surgically treated before irreversible retinal folds develop.     

Metalloproteinases as mediators of inflammation and the eyes: molecular genetic underpinnings governing ocular pathophysiology

There are many vision threatening diseases of the eye affecting millions of people worldwide. In this article, we are summarizing potential role of various matrix metalloproteinases (MMPs); the Zn (2+)-dependent endoproteases in eye health along with pathogenesis of prominent ocular diseases such as macular degeneration, diabetic retinopathy, and glaucoma via understanding MMPs regulation in affected patients, interactions of MMPs with their substrate molecules, and key regulatory functions of tissue inhibitor of metalloproteinases (TIMPs) towards maintaining overall homeostasis.     

The use of intravitreal gas for the treatment of ocular hypotony after glaucoma filtration surgery.

Hypotonous maculopathy is a serious complication of glaucoma filtration surgery. A patient with hypotonous maculopathy due to excessive filtration was treated with intravitreal gas. During the next several months, the intraocular pressure increased and the visual acuity improved. Intravitreal gas is useful for the treatment of hypotonous maculopathy due to excessive aqueous filtration.     

严重眼外伤Ⅰ期术后低眼压的处理及预后

目的探讨危重眼外伤Ⅰ期术中或术后应用全氟丙烷(C3F8)气体对眼压及其预后的影响。方法危重眼外伤26例(26眼)Ⅰ期术中或术后注入纯全氟丙烷气体,观察眼压并于Ⅱ期术中观察气体作用效果及预后评价。结果注气术后眼压得到改善23眼,18眼角膜水肿浑浊经气体充填后恢复透明15眼,Ⅱ期术中在气体作用下视网膜平复状态共21眼。术后随诊3~12月,视力提高22眼,视力不变3眼,视力下降1眼。结论危重眼外伤Ⅰ期术中或术后应用全氟丙烷气体能有效提升眼压同时取得较好预后。     

Topical ibopamine and corticosteroids in the treatment of post-surgery ocular hypotony

Purpose: The aim of the present preliminary study, performed on post-surgical hypotony, was the evaluation of the effects on ocular hypotony of the concomitant administration of ibopamine and corticosteroids. Methods: 14 patients (11 males — 3 females; mean age 47 years) with ocular hypotony following several vitroretinal surgical intervention in different districts, were enrolled. The inclusion criteria were: mean IOP during tonometric curve equal or lower than 6 mmHg, stable IOP for at least 60 days, ongoing treatment with 0.1% dexamethasone (4 times/day), successful surgical intervention, 2% ibopamine (4 times/day) was added to the corticosteroid therapy for 30–60 days. Results: Before ibopamine administration, mean IOP was 4.07 mmHg SD 1.71. At the end of the treatment period, mean IOP increased by 89% in comparison to baseline values (+ 3.64 mmHg SD 5.57). This difference was statistically significant (paired t = 2.39; P = 0.03). One month after ibopamine-treatment discontinuation, mean IOP decreased to pre-treatment values (4.86 mmHg SD 3.50). Conclusions: The results of the present study, although preliminary, suggest the possibility of a future pharmacological treatment of ocular hypotony with ibopamine, whose rationale is based on the increase of aqueous humor production by stimulating the D1 dopaminergic receptor.     

The ocular pharmacokinetics of topical diclofenac is affected by ocular inflammation.

The ocular pharmacokinetics of topical diclofenac sodium was studied in two experimental models of ocular inflammation and compared to physiological conditions. Keratitis or uveitis were induced by intrastromal injection of clove oil or by intravitreal lipopolysaccharide in rabbits. The control eyes were not inflamed. Simultaneously to the induction of inflammation, 30 microl of 0.1% diclofenac were applied topically in the right eye. Diclofenac levels were measured by HPLC in the cornea, aqueous humor (AH), iris/ciliary body (ICB) and plasma 30 min, 1, 3, 6 and 12 h after application. In physiological conditions, diclofenac reached a peak level in the cornea and ICB at 30 min slowly decreasing afterwards. Low levels of diclofenac were found in AH. In keratitic eyes, two peak levels which were significantly higher than in the controls were found in the cornea 30 min and 3 h after application. Diclofenac concentrations in keratitic AH and ICB were lower than in controls. In uveitic eyes, corneal and ICB levels peaked at 30 min, being significantly higher than in controls, and decreased quickly to very low levels at 1 h after application. In uveitic AH, diclofenac levels were lower than in controls. Plasma levels were very low (less than 0.1 microg/ml) in all experimental groups. It is concluded that the ocular pharmacokinetics of topical diclofenac is affected by inflammatory processes in the eye, reaching higher levels in the target tissues.     

The use of autologous fibrinogen concentrate in treating ocular hypotony after glaucoma filtration surgery.

Antimetabolite therapy with 5-fluouracil (5-FU) or mitomycin-C (MMC) has significantly improved the success rate of glaucoma filtration surgery. However, in some eyes, when filtration is excessive, persistent hypotony may develop. In this study, we describe the experience of using autologous fibrinogen concentrate (AFC) to treat patients with persistent hypotony after glaucoma filtration surgery. Among seven MMC-augmented trabeculectomy patients who developed persistent postoperative hypotony, the effects of AFC intrableb injections were evaluated. Under a microscope, 0.2 ml AFC and bovine thrombin were injected into the blebs of the patients from both sides of the filtering blebs. Postoperative best-corrected visual acuity, anterior chamber status, intraocular pressure (IOP) and fundus examination were followed and compared with those preoperative. On the second day, the mean IOP of seven eyes elevated from preoperative 3.4 +/- 2.1 mmHg to 12.6 +/- 4.2 mmHg, and the anterior chamber became deep without obvious inflammatory response. Within two weeks, macular edema and visual acuity were noted to improve in six eyes (85.7%). In addition, after a mean follow-up of 25 months, the trabeculectomy procedure remained successful in all eyes. AFC appears to be safe and effective in the treatment of ocular hypotony after glaucoma filtration surgery.     

Role of leukocytes in ocular inflammation of tyrosinemia II

In the animal model of tyrosinemia II only corneas from tyrosine(tyr)-fed rats produce chemoattractants in organ culture. To study the role of neutrophils (PMNs) in production of these chemoattractants, leukocytes (WBCs) were depleted using i.p. cyclophosphamide (CP). Saline (SAL)-treated rats maintained 18,375 +/- 894 WBC/mm3 (mean +/- SEM) with 4168 +/- 424 PMNs. Rats receiving CP (150 mg/kg day 0, 75 mg/kg day 4) has 1565 +/- 170 WBC (565 +/- 129 PMN) on day 3, and 398 +/- 68 WBC (19 +/- 5 PMN) on day 8. Rats ate a low-protein +/- 5% tyr diet on days 4-8. Only SAL-treated tyr-fed rats developed plaque-like gray epithelial lesions; histopathology showed corneal epithelial necrosis, stromal edema, and epithelial and stromal PMN infiltration. Control and CP-treated tyr-fed rat corneas showed no inflammation. On day 8 corneas were cultured in RPMI 1640 + 5% heat-inactivated fetal bovine serum. After 3 days, supernatants were assayed for chemotactic activity (leading front method); data were expressed as the percentage of peritoneal PMN migration relative to 5% zymosan-activated rat serum. The mean total migration toward 75% supernatant from SAL-treated, tyr-fed rat corneas was 79%, whereas migration toward corneal supernatants from controls and CP-treated tyr-fed rats ranged from 42-48%. Corneal extracts were assayed for proteolytic activity. WBC depletion prevented the increase in cathepsin B- and D-like activities present in tyr-fed corneas, suggesting that PMNs were a major source of these enzymes. The data suggest that WBC depletion reduces both corneal inflammation in vivo and the production of chemotactic activity by tyr-fed corneas in culture.     

Treatment of uveitis-associated refractory ocular hypotony with topical ibopamine

BACKGROUND: Ibopamine is a non-selective dopamine- and adrenalin-receptor agonist that has been shown to cause pupillary dilation and an increase in aqueous humour secretion. This novel drug can be used as a mydriatic agent, as a provocative test in open-angle glaucoma, and for the treatment of persisting ocular hypotony. HISTORY AND SIGNS: This 47-year-old man had a history of uveitis associated with Crohn's disease. Six years after deep sclerectomy for uveitic secondary glaucoma, he developed severe hypotony in his left eye with drop of visual acuity (VA). The hypotony did not respond to topical steroid treatment. 2 % Ibopamine solution was ordered t. i. d. concomitant to 1 % prednisolone acetate. THERAPY AND OUTCOME: Intraocular pressure (IOP) began to rise after 3 weeks of Ibopamine treatment and returned to normal (12 mmHg) with continuous recovery of VA after 8 weeks. Ibopamine was discontinued at an IOP of 16 mmHg after a course of 12 weeks. IOP and VA remained stable during the 12-month follow-up period. CONCLUSIONS: Ibopamine 2 % eye drops in combination with topical steroids are a therapeutic option in uveitis-associated ocular hypotony.     

巩膜缝线固定后房型人工晶状体术后低眼压的处理

目的探讨复杂性视网膜病变及严重眼外伤进行晶状体切除及玻璃体切除术的患者,Ⅱ期巩膜缝线固定人工晶状体植入术后低眼压的发生原因及其处理方法。方法回顾性分析于2003年6月至2004年12月作者早期开展Ⅱ期巩膜缝线固定人工晶状体植入术共34例(34眼),其中3眼是虹膜隔型人工晶状体,6眼同期行虹膜修补瞳孔成形术。结果本组34眼中有8眼(23.53%)术后发生低眼压,其中4眼为一过性低眼压,术后5~7 d前房黏弹剂再注入后,眼压逐渐恢复正常;另4眼伴有脉络膜脱离,其中3眼经皮质类固醇治疗后眼压恢复,1眼术后10 d行脉络膜上腔放液及注气术,眼压恢复。术后视力提高者32眼(94.1%)。随访6~18个月,人工晶状体均无明显倾斜偏位,视网膜脱离无复发。结论对于复杂性视网膜病变及严重眼外伤进行晶状体切除及玻璃体切除的患者,Ⅱ期巩膜缝线固定人工晶状体植入,术后低眼压是较易发生的并发症,经治疗可以恢复。     

Anterior segment inflammation and hypotony after posterior segment surgery

Recent advances in the instrumentation and surgical techniques for posterior segment surgery permit better anatomic and functional outcomes. Nevertheless, these procedures may be associated with complications involving the anterior segment, including postoperative inflammation and hypotony. One must differentiate infectious from noninfectious inflammation to initiate appropriate therapy promptly. Hypotony is a frustrating problem because it is difficult to reverse. The exclusion of eyes with other known causes of hypotony is important before establishing the putative mechanism of tractional ciliary body detachment caused by epiciliary proliferative tissue.     

Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

Progressive hemifacial atrophy (PHA) is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.     

The ocular microbiome and microbiota and their effects on ocular surface pathophysiology and disorders

The ocular surface flora perform an important role in the defense mechanisms of the ocular surface system. Its regulation of the immunological activity and the barrier effect against pathogen invasion are remarkable. Composition of the flora differs according to the methods of investigation, because the microbiome, composed of the genetic material of bacteria, fungi, viruses, protozoa, and eukaryotes on the ocular surface, differs from the microbiota, which are the community of microorganisms that colonize the ocular surface. The observed composition of the ocular surface flora depends on harvesting and examining methods, whether with traditional culture or with more refined genetic analysis based on rRNA and DNA sequencing. Environment, diet, sex, and age influence the microbial flora composition, thus complicating the analysis of the baseline status. Moreover, potentially pathogenic organisms can affect its composition, as do various disorders, including chronic inflammation, and therapies applied to the ocular surface.A better understanding of the composition and function of microbial communities at the ocular surface could bring new insights and clarify the epidemiology and pathology of ocular surface dynamics in health and disease. The purpose of this review is to provide an up-to-date overview of knowledge about this topic.     

Effects of experimental ocular inflammation on ocular immune privilege.

PURPOSE: To determine whether the inflammation of endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) alters key in vivo and in vitro parameters of ocular immune privilege. METHODS: For EIU induction, C3H/HeN mice received 200 microg lipopolysaccharide (LPS). For EAU induction, B10.A mice were immunized with 50 microg interphotoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell proliferation. Eyes with EAU were assessed for the capacity to support anterior chamber (AC)-associated immune deviation (ACAID) induction after injection of ovalbumin (OVA). RESULTS: Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH promptly lost its capacity to suppress T-cell proliferation and became mitogenic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 days and continued to remain elevated thereafter. Whereas 11-day EAU AqH failed to suppress T-cell proliferation, AqH at later time points reacquired immunosuppressive properties. Injection of OVA into the AC of eyes of mice with EAU failed to induce ACAID. CONCLUSIONS: The intraocular inflammation of EIU and EAU disrupted important parameters of immune privilege, ranging from breakdown of the blood- ocular barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate immune expression and inflammation can be a property even of inflamed eyes.     

Attempt to arrest eye growth by means of ocular hypotony

Attempt to retard growth of the eye in 4 young rabbits by means of prolonged ocular hypotony maintained by timolol-maleate were not successful. The eyes treated with 0.5 timolol twice a day showed a sustained hypotensive response of 4-5 mm Hg which lasted for the 4 months experimental period. No significant differences in size and on rate of growth in the treated and the untreated eyes were noted. In fact, over the 4 months postnatal period, both groups of eyes increased 0.5 mm per week in axial length. Our experiment suggests that in developing rabbit eyes, at least reduction of IOP is not a factor in effecting a smaller globe.     

Prostaglandins and ocular inflammation

Evidence for prostaglandins as mediators of some inflammatory responses is briefly, but critically discussed. The hypothesis that prostaglandins are mediators of ocular inflammation is presented and discussed according to the tenets of Miller & Melmon (1970). Prostaglandins are released after mechanical stimulation, paracentesis, laser irradiation, (non)-immunogenic uveitis in experimental animals, and in patients with acute anterior uveitis. Prostaglandins were neither found after antidromic stimulation of the trigeminal nerve, oculomotor nerve stimulation, intracameral formaldehyde, topical nitrogen mustard, nor in patients with open angle glaucoma.Administering of prostaglandins produces transient ocular hypertension, increased vascular permeability and miosis. Ocular hypotension has been shown to follow the hypertensive response. Hypertension is considered to be due to a breakdown of the blood-aqueous barrier of the ciliary processes and iris. Prostaglandins of the E series are the most potent, and species differences occur. Prostaglandin E₁ potentiates the histamine-induced increase in vascular permeability of the conjunctiva, but not the uvea. Polyphloretin phosphate aspecifically blocks the ocular actions of prostaglandins. Non-steroidal anti-inflammatory drugs inhibit prostaglandin synthetase and the ocular effects of arachidonic acid, its substrate. Prostaglandins are poorly catabolised by the eye, but are removed from ocular fluids by a transport mechanism in the anterior uvea. This becomes inoperative in (non)-immunogenic uveitis in rabbits allowing prostaglandins to accumulate. Anti-inflammatory steroids decrease the availability of arachidonic acid for prostaglandin synthetase. Intermediates formed in the biosynthesis of prostaglandins may well be more important in inflammation than the prostaglandins themselves.Part of this review was presented at the 171st Congress of the Dutch Ophthalmological Society.