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Inhibition of fibroblast proliferation by human iris pigment epithelial cells in vitro: preliminary results.

BACKGROUND: The interaction between different cells plays an important role in many physiological and pathological processes. Since the proliferation of fibroblasts is very much involved in the pathogenesis of eye diseases such as proliferative vitreoretinopathy, the failure of filtration in glaucoma surgery, etc., we attempted to ascertain whether iris pigment epithelial cells (IPE) have some modulating effect on fibroblast proliferation. METHODS: Human IPE were explanted and the third-passage culture was transferred into serum-free RPMI-1640 medium. After 48 h of further incubation, the medium was collected and submitted to centrifugation; the supernatant was used as the conditioned medium of IPE (IPE-CM). Cultured fibroblasts from Tenon's capsule were seeded in a 96-well plate and incubated with IPE-CM in different concentrations. The proliferation of fibroblasts was estimated by thymidine incorporation and cell counting. RESULTS: The incorporation of tritiated thymidine by fibroblasts was reduced to 56.68% of baseline with 1:16 diluted IPE-CM and to 13.63% and 8.20%, respectively, with 1:8 and 1:2 diluted IPE-CM. These findings were in good accordance with the results of cell counting, performed in parallel. SDS-PAGE of IPE-CM revealed two specific bands with molecular weight 65 kDa and 40 kDa. CONCLUSION: IPE-CM showed an obvious dose-dependent inhibitory effect on fibroblast proliferation and was presumed to contain some active factors contributing to this effect.

Cell Count↗

Traumatic dislocation of the globe into the maxillary sinus associated with extraocular muscle injury.

BACKGROUND: The mechanism of complete dislocation of an intact globe into the maxillary sinus after an extensive blowout fracture has not been clearly documented. METHODS: A 68-year-old man sustained orbital wall fractures of the right orbit, resulting in dislocation of the globe into the maxillary sinus, associated with the transection of the medial and inferior rectus (MR and IR). We repaired the orbital wall fractures using Medpor barrier sheets, and repositioned the dislocated globe. And then, the distal section of the IR was sutured at its proximal end and the severed distal section of the MR was sutured at the fascial sheath and Tenon's capsule. RESULTS: After repositioning, the eyeball was intact without signs of perforation, but the patient's visual acuity was impaired, exhibiting a loss of light perception, coupled with a noted pallor of the optic disc. The patient's eye movement was severely restricted, but supraduction and abduction proved possible. CONCLUSIONS: This case demonstrates that the globe can be dislocated into the maxillary sinus following orbital wall fracture associated with extraocular muscle injury, and provides a clue into the mechanism underlying dislocation of the globe into the maxillary sinus.

Aged↗

Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C.

PURPOSE: To evaluate the potential of the vitamin E compound alpha-tocotrienol as antifibrotic agent in vitro. METHODS: Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms alpha-tocopherol, alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5 min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24 h. RESULTS: alpha-Tocopherol and alpha-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by alpha-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to alpha-tocopheryl succinate, 50 microM or repeatedly 20 microM of alpha-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400 microg/ml showed a stronger antiproliferative effect than alpha-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. CONCLUSIONS: Of the vitamin E forms tested, only alpha-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of alpha-tocotrienol.

Aged↗

Real-time imaging of transscleral diode laser cyclophotocoagulation by optical coherence tomography.

PURPOSE: To present optical coherence tomography (OCT) for real-time imaging of cyclophotocoagulation effects. METHODS: In a pilot study, real-time transscleral OCT images were generated during diode laser cyclophotocoagulation in four eyes of four patients suffering from uncontrolled glaucoma using a specially designed contact applicator containing the OCT fiber, a focussing fiber optic and the fiber of the diode laser. RESULTS: When the contact system was used, two layers could be differentiated: a superficial thick hyperreflective complex representing conjunctiva, Tenon's capsule, episclera and sclera, and a thinner hyporeflective layer representing the ciliary body. During cyclophotocoagulation, real-time OCT showed a clear and sudden thickening of the ciliary body in the treated area. CONCLUSION: This new OCT device represents a first step towards visual, real-time imaging of cyclophotocoagulation. After further adaptation of the delivery system, further trials are needed to correlate OCT findings with aqueous production and intraocular pressure.

Ciliary Body↗

A pilot study on slit lamp-adapted optical coherence tomography imaging of trabeculectomy filtering blebs.

BACKGROUND: Our study aims to identify anatomical characteristics of glaucoma filtering blebs by means of slit lamp-adapted optical coherence tomography (SL-OCT) and to identify new parameters for the functional prognosis of the filter in the early post-operative period. METHODS: Patients with primary open-angle glaucoma, aged 18 years and older, scheduled for primary trabeculectomy at the Department of Ophthalmology, Radboud University Nijmegen Medical Centre, were considered for our study. All patients underwent standardized trabeculectomy with intra-operative application of mitomycin C. The filtering blebs were evaluated clinically and with SL-OCT on day 1 and 1, 2, 4 and 12 weeks following surgery. The resulting data were analysed and weighed against surgical success. To better understand the SL-OCT data a small comparative histologic study was performed. RESULTS: The study included 20 eyes of 20 patients. After completion of our study, 15 eyes of 15 patients (mean age+/-SD 67 +/- 16 years) were eligible for data analysis and 5 eyes missed at least one follow-up visit. Filtering surgery was considered successful (intraocular pressure < or = 21 mmHg without antiglaucomatous medication) in 11 of 15 eyes. SL-OCT frequently demonstrated multiple hypo-reflective layers within Tenon's capsule ("striping" phenomenon) in the first post-operative week. Presumably, these layers corresponded with drainage channels in the histological specimen. These channels were present in functional filters but not in the failures. In addition, the visualisation of the sclera below the filtering zone was better defined in failures compared with successful filtering blebs ("shading" phenomenon). We observed no differences in the volume and clinical aspect of the blebs in the successful group compared with the unsuccessful group. CONCLUSIONS: Successful filtering blebs show characteristic optical properties on SL-OCT. These phenomena suggest a diffusely enhanced fluid content and the presence of intra-bleb drainage channels in functional filtering blebs.

Aged↗

Delayed-onset streptococcus pyogenes endophthalmitis following Ahmed glaucoma valve implantation.

BACKGROUND: To report a case of delayed-onset Streptococcus pyogenes endophthalmitis following implantation of an Ahmed glaucoma valve. CASE: A 10-year-old patient presented with acute endophthalmitis 1 year after Ahmed glaucoma valve implantation. OBSERVATIONS: The conjunctiva and Tenon's capsule over the valve plate had been penetrated by one of the polypropylene fixation sutures. The valve was removed, and pars plana vitrectomy was performed. Vitreous specimens and removal of the discharge over the plate revealed Streptococcus pyogenes. CONCLUSIONS: This is the first documented case of Streptococcus pyogenes endophthalmitis following Ahmed glaucoma valve implantation. We think the conjunctival buttonhole caused by the polypropylene suture provided an entry site for the infection.

Child↗

Aqueous humor-stimulated protein biosynthesis in ocular tissue fibroblast culture.

Dilute concentrations of aqueous humor stimulate DNA synthesis and cell division in monolayer fibroblast culture of rabbit skin and human and rabbit Tenon's capsule. We used [35S]-methionine to study 20% aqueous humor's effect on protein biosynthesis. A non-specific stimulator, 10% fetal bovine serum, was also used for comparison. Incorporation of radioactivity into acid-precipitable material was measured in both the fibroblasts and the media containing extracellular labeled proteins. The extracellular and intracellular labeled proteins were resolved by gel electrophoresis. Both 20% aqueous humor and 10% fetal bovine serum stimulated increased incorporation of [35S]-methionine into intracellular proteins relative to control values (from fibroblasts maintained in 0.5% fetal bovine serum-supplemented medium). However, 20% aqueous humor caused only a slight increase in labeling of proteins exported into the medium, whereas 10% fetal bovine serum stimulated a several-fold increase in extracellular labeled proteins relative to control values. Gel electrophoresis of labeled proteins showed that the quantitative distribution of extracellular proteins varied depending on the growth stimulator present. We conclude that the protein biosynthesis modulation by aqueous humor differs from that by fetal bovine serum. Aqueous humor may selectively stimulate the synthesis of discrete proteins while a general stimulation occurs with fetal bovine serum.

Animals↗

Effect of varying oxygen concentrations on the proliferation of retinal microvascular cells in vitro.

Microvascular fragments and pure cultures of either retinal microvascular endothelial cells, retinal pericytes or Tenon's capsule fibroblasts were grown on a gas permeable substrate while exposed to varying oxygen concentrations (5, 10, 20, 40 and 95% oxygen). For all three cell types cell proliferation was greatest under the lowest oxygen concentration and decreased as the oxygen concentration increased. The decrease in the proliferative ability of cells exposed to the higher oxygen concentrations could be reversed if the cells were returned to a normoxic environment. Endothelial cells were the most sensitive to changes in oxygen tensions showing a proliferative response after 24 hr exposure as opposed to 48 hr for pericytes and fibroblasts. These results suggest a direct mechanism by which the intra-vitreal and intra-retinal oxygen tension may influence both the development of preretinal new vessels (in response to retinal ischaemia) and also the regression of neovascularization following scatter photocoagulation or vitrectomy.

Animals↗

Long-term follow-up results of a pilot trial of a fluocinolone acetonide implant to treat posterior uveitis.

PURPOSE: To investigate the safety and efficacy of a fluocinolone acetonide intravitreal implant in the treatment of noninfectious posterior uveitis. DESIGN: Noncomparative interventional case series, dose randomized, dose masked, prospective. PARTICIPANTS: Thirty-six eyes of 32 patients with a history of recurrent noninfectious posterior uveitis. METHODS: Patients were randomized to receive either a 0.59-mg or a 2.1-mg fluocinolone acetonide intravitreal implant. Patients were observed every 4 to 6 weeks for the first 3 months and then every 3 months thereafter. MAIN OUTCOME MEASURES: Preoperative and postoperative ocular inflammation, visual acuity (VA), antiinflammatory medication use, and safety. RESULTS: Mean follow-up duration was 683+/-461 days (range, 204-1817). Mean baseline visual acuity for the device-implanted eyes was +1.1 logarithm of the minimum angle of resolution (logMAR) units (20/250), which improved significantly to +0.81 logMAR units (20/125) at 30 months (P<0.05). Inflammation was effectively controlled over the follow-up period. The average number of recurrences in the 12 months before implantation was 2.5 episodes per eye. None of these eyes experienced a recurrence for the first 2 years after implantation. There was a reduction in systemic and local therapy use in the device-implanted eyes; of the patients who remained on systemic medication after implantation, dosage was reduced in 68%. The posterior sub-Tenon's capsule injection rate significantly decreased from a mean of 2.2 injections per eye per year to 0.07 injections per eye per year (P<0.0001) The most common adverse event was intraocular pressure (IOP) rise. At baseline, 11.0% of eyes used pressure-lowering agents, versus 56.1% over the follow-up period (P = 0.005). Filtering procedures were performed in 7 (19.4%) eyes. Four of the 8 phakic eyes, each of which had some level of cataract at device implantation, subsequently underwent cataract extraction. There were no device explantations or patients lost to follow-up during the investigation. CONCLUSION: The fluocinolone acetonide intravitreal implant effectively controlled intraocular inflammation in the studied population. Elevated IOP and cataracts that occurred in fluocinolone device-implanted eyes were managed by standard means. The fluocinolone acetonide sustained drug delivery implant seems to be promising in patients with posterior uveitis who do not respond to or are intolerant to conventional treatment.

Adolescent↗

Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration.

PURPOSE: To compare 1-year safety and efficacy of anecortave acetate 15 mg with photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT treatment. DESIGN: Prospective, masked, randomized, multicenter, parallel group, active control, noninferiority clinical trial. PARTICIPANTS: Five hundred thirty patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration were randomized to treatment with either anecortave acetate 15 mg or PDT. METHODS: In the anecortave acetate group, the drug was administered under the Tenon's capsule as a periocular posterior juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the first administration of anecortave acetate, patients in this treatment group received a sham PDT treatment, and sham PDT treatments were repeated every 3 months if there was evidence of leakage on fluorescein angiography (FA). Patients assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed based upon FA, and a sham PJD procedure at the beginning of the study and at month 6. Best-corrected visual acuity was determined at baseline and all follow-up visits. Safety data were regularly reviewed by an independent safety committee. MAIN OUTCOME MEASURE: Percent responders (patients losing <3 lines of vision) at month 12. RESULTS: Percent responders in the anecortave acetate and PDT groups were 45% and 49%, respectively (not statistically different, P = 0.43). The confidence interval (CI) for the difference ranged from -13.2% favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome for anecortave acetate was improved in patients for whom reflux was controlled and who were treated within the 6-month treatment window (57% vs. 49%; 95% CI, -4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse events related to the study drug were reported in either treatment group. CONCLUSIONS: The safety and efficacy outcomes in this study demonstrate that the benefits of anecortave acetate for the treatment of choroidal neovascularization outweigh the risks associated with either the drug or the PJD administration procedure.

Aged↗

Trabeculectomy with mitomycin C for refractory glaucoma in blacks.

The use of one intraoperative application of mitomycin C at the filtration site has been effective in eyes at increased risk for failure of routine trabeculectomy. To study the efficacy and safety of this technique in patients with refractory glaucoma, we prospectively examined 30 eyes of 26 black patients in whom a 0.2-mg/ml solution of mitomycin C was applied between Tenon's capsule and the sclera for five minutes before trabeculectomy. The results were compared to those found in a matched group of 30 eyes of 28 patients who underwent trabeculectomy without mitomycin C. The mean postoperative intraocular pressures were significantly lower in the mitomycin C group than in the control group (P = .001). Of the 30 eyes in the mitomycin C group, 25 (83%) had an intraocular pressure of less than 21 mm Hg without glaucoma medication, compared to 11 of 30 (37%) in the control group (P = .00006). In the mitomycin C group, 19 eyes (63%) developed a cystic avascular thin-walled filtering bleb, four eyes (13%) a late positive Seidel test, and one eye slight scleral thinning over the area where the mitomycin C was applied. Although mitomycin C is effective when used in this manner, further study is required to determine the long-term complications.

Adult↗

Massive epithelium-lined inclusion cysts after scleral buckling.

Two patients with massive epithelium-lined inclusion cysts of the orbit became symptomatic five and 16 years after scleral buckling. Each patient described diplopia and displacement of the previously treated eye. An orbitotomy in the first patient disclosed a loculated epithelium-lined inclusion cyst that extended posteriorly from the insertion of the inferior rectus muscle nearly to the apex of the orbit. In the second patient, a loculated epithelium-lined inclusion cyst extended into the superior nasal portion of the orbit from its origin near the insertions of the superior and medial recti muscles. We speculated that epithelial cells of the conjunctiva were shed at the time of scleral buckling and became lodged in the exposed sulcus created by the surgical retraction of Tenon's capsule. Here they proliferated and formed the large epithelium-lined cysts. In each patient, removal of the cyst was followed by a decrease in diplopia as the displaced globe returned toward its normal position.

Aged↗

Chronic fibrous tenonitis with vitreous hemorrhage and choroidal indentation.

A 45-year-old white man had a bulbar subconjunctival mass, eyelid edema, and choroidal indentation. Biopsy of the subconjunctival mass revealed acute and chronic inflammation. One year later a spontaneous vitreous hemorrhage, choroidal folds, increased choroidal indentation, and serous retinal detachment were present. B-mode ultrasonography, operative findings, and biopsy revealed a chronic inflammatory mass with fibrosis confined to Tenon's capsule. Initial treatment with systemic corticosteroids resulted in no improvement, but mild progression occurred when the corticosteroids were tapered. Improvement occurred to the previous level of involvement when corticosteroids were reinstituted.

Choroid↗

Generalized fibrosis of the extraocular muscles.

We studied four patients with the general fibrosis syndrome. One patient had bilateral inguinal hernias and unilateral cryptorchism; the other patients had no other congenital abnormalities. The patients developed normally both neurologically and metally. We successfully treated amblyopia and achieved good functional and cosmetic results with strabismus and blepharoptosis surgery. Histopathologic study revealed fibrous infiltration of extrinsic eye muscle and Tenon's capsule without inflammatory changes.

Amblyopia↗

Comparative efficacy of antiviral drugs on human ocular fibroblasts.

The effects of several antiviral drugs on fibroblast attachment and proliferation from human Tenon's capsule were investigated. These drugs included purine nucleoside analogs, vidarabine and acyclovir (ACV); pyrimidine nucleoside analog, AZT; and a synthetic cyclic primary amine, amantadine. Fibroblast attachment and proliferation inhibition were determined by Coulter counter, a colorimetric assay of the enzyme hexosaminidase, and a 3H-thymidine uptake assay. Amantadine and AZT inhibited fibroblast attachment at concentrations higher than 6.61 x 10(-4)M and 3.73 x 10(-4) M, respectively. Amantadine and AZT had inhibitory effects on fibroblast proliferation as early as day 1, whereas vidarabine and ACV manifested their inhibitory effects after day three by Coulter counter and hexosaminidase assays. For amantadine, AZT, ACV and vidarabine, the 50% inhibitory dose (ID50) were 4.94 x 10(-5) M, 1.26 x 10(-5) M, 4.60 x 10(-4) M, and 1.52 x 10(-5) M at day 9, respectively, as measured by 3H-thymidine uptake assay. All four antiviral agents tested had inhibitory effects on human ocular fibroblast proliferation and their inhibitory potential decreased in the order of amantadine > or = vidarabine > AZT > or = ACV.

Acyclovir↗

Exposure of tantalum mesh orbital implants.

This retrospective study of 195 enucleations with tantalum mesh implants reviews the role of demographic, preoperative, and operative factors in subsequent implant exposure or extrusion. Fourteen implants (7.2%) became exposed, two of which subsequently extruded. Significant associations were found between implant exposure and history of prior orbital infection, and suturing of the inferior oblique to the lateral rectus muscle. The average age at enucleation was 20.4 years for those whose implant became exposed, which was significantly less than the average age of 38.7 years for those without exposure of the implant. No association was found between implant exposure and gender, preoperative diagnosis, proptosis, chemosis, sharp trauma to the orbit, orbital fracture, previous orbital surgery, implant size, closing of posterior Tenon's capsule, or muscles sutured to the implant. Because of the high exposure rate, it is recommended that the use of tantalum mesh implants be discontinued.

Adult↗

The fat adherence syndrome and strabismus after retina surgery.

The etiology of persistent strabismus after retina surgery has been poorly understood. Seven patients with acquired restrictive strabismus after retina surgery were surgically explored for the cause of the strabismus. In each case, the fat adherence syndrome was identified as playing a significant role in causing the restriction. In four patients, restriction secondary to the fat adherence syndrome was the sole cause of the strabismus. Other contributing causes included a misplaced muscle in two patients and a sponge under a muscle in one patient. Our conclusion is that the fat adherence syndrome is an important cause of restrictive strabismus after retina surgery and that this complication can be minimized by avoiding surgical maneuvers that violate Tenon's capsule and expose extraconal fat.

Adipose Tissue↗

A new classification of superior oblique palsy based on congenital variations in the tendon.

BACKGROUND: Superior oblique palsy is the most frequent isolated cranial nerve palsy seen in strabismus practice. It is traditionally diagnosed according to etiology as acquired, congenital, or idiopathic, but surgical treatment is based on deviation not etiology. Observations at surgery led to speculation that the superior oblique tendon is different in congenital compared with acquired superior oblique palsy and that this difference should be considered in surgical treatment. METHODS: The authors reviewed the charts of 82 patients (89 eyes) undergoing surgery on the superior oblique tendon for superior oblique palsy. In each case, the palsy had been diagnosed preoperatively as acquired, congenital, or idiopathic, and, at surgery, characteristics of the tendon anatomy were described. RESULTS: Thirty-eight superior oblique tendons (36 patients), diagnosed as congenital superior oblique palsy, included 33 abnormal tendons and 5 normal tendons. Twenty-four tendons (21 patients), diagnosed as traumatic superior oblique palsy, included 22 normal and 2 abnormal tendons. Twenty-seven tendons (25 patients), diagnosed as idiopathic, included 19 normal and 8 abnormal tendons. Abnormal tendons were divided into 4 categories: (1) redundant, (2) misdirected, (3) inserted in posterior Tenon's capsule, and (4) absent. CONCLUSIONS: The authors conclude that congenital superior oblique palsy is usually associated with a structural abnormality of the superior oblique tendon (87%). Whereas acquired superior oblique palsy usually has a normal tendon (92%). Superior oblique underaction in acquired superior oblique palsy results from a neural deficit. Potential variance in anatomy of the superior oblique tendon should be considered when undertaking surgery for superior oblique palsy.

Adolescent↗