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Trabeculectomy with 5-fluorouracil subsequent to circular buckling operation and cataract extraction.

Six patients, each with one eye that had previously undergone circular buckling surgery for the repair of retinal detachment before or followed by cataract extraction with or without intraocular lens implantation, underwent trabeculectomy with 5-fluorouracil (5-FU) for intractable glaucoma. Surgery was done through scarred subconjunctival tissues that were excised partially. The total doses of 5-FU ranged from 65 to 100mg (mean +/- standard deviation, 84.2 +/- 13.2mg) Eight to 47 months later, intraocular pressures were 18mmHg in five eyes, two of which were not receiving hypotensive medications. In the sixth eye, the intraocular pressure was 26mmHg with maximum hypotensive treatment. Intraocular pressures in the six eyes were significantly lower postoperatively than preoperatively (P < .05). This preliminary study suggests that filtering surgery with 5-FU may be beneficial after intraocular operations even in eyes where it is done through postoperative scarred subconjunctival tissues.

Adult↗

Prospective study of ab externo erbium:YAG laser sclerostomy in humans.

PURPOSE: To evaluate the efficacy of ab externo erbium:YAG (Er:YAG) laser sclerostomy in controlling intraocular pressure in eyes with uncontrolled glaucoma. METHODS: We performed ab externo laser sclerostomy on eyes of 26 patients. Mean +/- SD postoperative follow-up was 11.4 +/- 0.9 months. Complete success was defined as intraocular pressure below 22 mm Hg with no adjunct medication; qualified success was defined as intraocular pressure below 22 mm Hg with medication. RESULTS: In all eyes, ab externo Er:YAG laser sclerostomy achieved a functioning fistula with a prominent filtering bleb. Twelve eyes had had neodymium:YAG (Nd:YAG) laser iridotomy at the site of laser sclerostomy 2 weeks before filtering surgery; 14 eyes had surgical iridectomy at the site of laser sclerostomy. Mean preoperative intraocular pressure of 30.7 +/- 7.3 mm Hg (range, 17.0 to 48.0 mm Hg) was significantly (P < .05) reduced to 18.3 +/- 1.0 mm Hg (range, 0 to 25.0 mm Hg) at 2 weeks postoperatively. thereafter, marked regression was noted: at 1 month postoperatively, intraocular pressure was 20.1 +/- 9.5 mm Hg (range, 4.0 to 44.0 mm Hg); half-life of complete success was 25 days; of qualified success, 56 days; and of a functioning filtering bleb, 36 days. CONCLUSIONS: Ab externo Er:YAG laser sclerostomy reliably created successful full-thickness fistulae with prominent filtering blebs in human glaucomatous eyes. However, a transient phase of ocular hypotony caused by aqueous overfiltration, followed by an ongoing rate of fistula patency failure, renders Er:YAG laser sclerostomy, as performed in this study, unsuitable for long-term pressure control.

Adult↗

Amniotic membrane transplantation or conjunctival limbal autograft for limbal stem cell deficiency induced by 5-fluorouracil in glaucoma surgeries.

PURPOSE: To determine if human amniotic membrane transplantation or limbal stem cell transplantation is effective to restore the corneal surface with partial or total limbal stem cell deficiency, respectively, caused by 5-fluorouracil (5-FU) toxicity after glaucoma surgeries. METHODS: Partial and total limbal stem cell deficiency was confirmed by impression cytology as the cause of reduced vision and corneal surface breakdown in a 69-year-old man and a 67-year-old man, respectively, who both had received a total of 105 mg 5-FU injections. Amniotic membrane transplantation or conjunctival limbal autograft was performed for corneal surface reconstruction, respectively. RESULTS: For a period of 15 months of follow-up, the visual acuity improved, and their corneal surfaces remained avascular, smooth, and without recurrence of limbal stem cell deficiency. CONCLUSION: Limbal stem cell deficiency can occur as a late complication for patients receiving 5-FU after glaucoma filtering surgeries. Partial limbal stem cell deficiency can be treated with amniotic membrane transplantation alone, whereas limbal transplantation must be considered as an alternative for total limbal stem cell deficiency to restore the corneal surface integrity and vision.

Aged↗

Indications and technique for reopening closed filtering blebs using the Nd:YAG laser--a review and case series.

We reviewed the results of Nd:YAG laser treatment used with gonioscopy to reopen the internal sclerostomy in 10 consecutive patients with failing filtering blebs in whom the sclerostomy had become occluded internally with a membrane or iris after filtering surgery. Sixteen to 50 applications of 6- to 6.9-millijoules Nd:YAG laser irradiation were directed to the internal sclerostomy site. In 6 of the 10 patients, filtration was successfully reestablished, initially reducing the mean intraocular pressure (IOP) from 26.5 mm Hg (range, 20 to 40 mm Hg) to 8.6 mm Hg (range, 5 to 16 mm Hg), with an average IOP of 13.5 mm Hg at 7 months after the laser treatment. Nine of the patients were on significantly fewer glaucoma medications. We conclude that the YAG laser can be successfully used to reopen the fistula by the internal approach in carefully-selected patients who previously have had well-established filtering blebs. Identification of these suitable candidates involves careful gonioscopy.

Adult↗

The effects of subconjunctival verapamil on filtering blebs in rabbits.

BACKGROUND AND OBJECTIVE: Verapamil is a calcium antagonist that has been shown to modulate wound healing through multiple mechanisms. The wound modulating effects of verapamil were studied in a rabbit model of filtering surgery. MATERIALS AND METHODS: Twenty New Zealand albino rabbits underwent a fistulizing procedure, with either verapamil or saline injected subconjunctivally daily for 6 days following surgery. The animals were sacrificed at 20 days after the fistulizing procedure. The effectiveness of verapamil in modulating wound healing was evaluated by bleb patency testing, histology, measurement of scar thickness, and counts of bromodeoxyuridine (BrdU)-labeled cells at the sclerostomy site. RESULTS: The group treated with verapamil had a 44 percent patency rate compared with 10 percent in the control group (P < .05), a mean scar thickness of 195.96 +/- 68 mu m compared with 313.55 +/- 110.4 mu m in the control group (P < .02), and a mean BrdU-labeled cell count of 15.5 +/- 14.7 compared with 26.3 +/- 17.0 in the control group (P < .002). CONCLUSION: Verapamil was effective in reducing scar formation at the sclerostomy site. At the doses administered, verapamil appeared to modulate wound healing in filtering blebs in the rabbit model. Further studies are needed to determine the dose-response and the efficacy of the drug in nonhuman primates.

Animals↗

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation.

PURPOSE: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. SETTING: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. METHODS: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. RESULTS: Mean follow-up was 16.7 months +/- 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperatively, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). CONCLUSION: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Aged↗

A comparative study of small incision trabeculectomy avoiding tenon's capsule with conventional trabeculectomy.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the results of small incision trabeculectomy (SIT) avoiding Tenon's capsule vis-à-vis conventional trabeculectomy, and find a safe, effective alternative to conventional trabeculectomy with or without pharmacological wound modulation. PATIENTS AND METHODS: A controlled prospective study was conducted on 80 consecutive open-angle glaucoma patients requiring glaucoma filtration surgery. They were divided into two groups: Group I (n = 40): patients undergoing conventional trabeculectomy; and Group II (n = 40): patients undergoing limbal approach SIT. Patients were followed up serially for a minimum of 12 months and their intraocular pressure was monitored. Success of the procedure was defined as an intraocular pressure (IOP) <22 mm Hg with no additional antiglaucoma medication or surgery, and achieving at least a 30% reduction from the initial IOP at which optic disc cupping and/or visual field changes occurred. RESULTS: A significant fall (P <0.0001) in the final mean IOP was present in both groups at all time intervals in comparison to their preoperative values. The final mean intraocular pressure achieved with conventional trabeculectomy was 18.90 +/- 4.86 mm Hg versus 16.60 +/- 5.93 mm Hg with SIT. The final success rate of 90% was obtained with SIT vs 80% with conventional trabeculectomy. No major complications were encountered with either procedure although complications such as shallow anterior chamber and progression of cataractogenesis were seen more often in patients undergoing conventional trabeculectomy. CONCLUSION: Small incision trabeculectomy avoiding Tenon's capsule is a low-cost and safe alternative to conventional trabeculectomy that effectively reduces IOP in 90% of cases. The use of a small 2.5 mm limbal incision, which obviates the dissection of Tenon's capsule and absence of any major complication, suggests that this procedure be used more often in glaucomatous eyes needing filtering surgery.

Adult↗

Surgical management of epiretinal membrane in young patients.

PURPOSE: To report the outcome of epiretinal membrane (ERM) surgery in young patients. DESIGN: Interventional case series study. METHOD: A retrospective review of 20 young patients who had undergone vitrectomy and epiretinal membrane removal. All patients had a preoperative examination, including fundus biomicroscopy, red free photographs, and fluorescein angiography. RESULTS: Nine patients were males and 11 females (age: 7-26 years; mean: 16.3 years). Follow up ranged from 4-96 months (mean: 21.2 months). The 20 patients comprised 13 cases of idiopathic ERM, six cases in which ERM was associated with ocular inflammation and one case of combined hamartoma of the retina and retinal pigment epithelium (RPE). In 13 cases, the ERM was especially white, thick, and opaque, with localized constriction and severe retinal distortion. Final best-corrected visual acuity (VA) was significantly better than preoperatively (20/50 vs. 20/112), (P = 0.0002). Mean improvement in VA was 4.25 lines and 17 patients gained two or more lines. This improvement was better in secondary than idiopathic ERM (6 lines vs. 3.3). During follow up, five cases of recurrence were observed (25%). In another case, postoperative persistent ocular hypertension required filtering surgery. CONCLUSION: The characteristics of ERM in young patients are quite different in many cases from those in adults in terms of thickness and adherence. Removal of ERM in young patients is feasible and safe although the membrane may focally adhere strongly to retinal vessels. VA usually improves significantly after surgery, but recurrences are more frequent than in adults.

Adolescent↗

[Frequency and risk factors of intraocular pressure increase after penetrating keratoplasty].

PURPOSE: The aim of this study was to evaluate the incidence, risk factors and management of glaucoma following penetrating keratoplasty (PK) and to check for possible correlations with the indication for PK. PATIENTS AND METHODS: 534 eyes of 483 patients (age 54.7 +/- 19.8 years), that had undergone PK from 1989 to 1999 were retrospectively analyzed. The mean follow-up was 2.7 +/- 1.8 years. According to the type of surgical procedure patients were classified in 5 groups: group 1) PK only (n = 291); group 2) PK combined with extracapsular cataract extraction and intraocular lens (IOL) implantation (n = 124); group 3) PK combined with secundary IOL-implantation or IOL-change (n = 32); group 4) PK only after previous cataract surgery (n = 55) and group 5) Cataract surgery after PK (n = 32). The trephination was performed from the epithelial side in donor and recipient either by nonmechanical trephination with the 193 nm excimer laser (n = 444) or mechanical trephination (n = 90). An iridotomy was performed routinely during PK. The postoperative treatment with topical steroids was standardized. RESULTS: Preoperatively, glaucoma was diagnosed in 3.2% for all patients with groups 3 und 4 showing a significantly larger number of glaucomatous eyes (15.6% and 18.9%). Most of the mild early intraocular pressure elevations in group 1 (3.4%) and group 2 (3.0%) were controlled after 6 months (0.5% and 1.1%). Groups 3 and 4 showed most frequently increased intraocular pressure and/or antiglaucomatous treatment (21.4% and 18.7%) six weeks postoperatively. Patients in all groups showed no higher prevalence of persistent glaucoma from six months postoperatively than preoperatively throughout the follow-up period. Again groups 3 and 4 presented the largest number of persistent glaucoma. In most eyes the IOP was controlled by topical antiglaucomatous treatment. Serious forms seen in 2 patients with anterior synechiae caused by anterior chamber lens required several filtering surgeries or pars plicata diathermy, respectively. One patient with pseudoexfoliation syndrome required laser trabeculoplasty. The so-called "Urrets-Zavalia syndrome" was seen in none of the patients. CONCLUSION: The development of increased intraocular pressure after PK varied with the indication for keratoplasty. Postkeratoplasty glaucoma seems to be strongly associated with preexisting anterior synechiae and/or simultaneous anterior chamber lens implant removal. Intraoperative iridotomy can prevent the development of acute angle closure glaucoma after keratoplasty.

Adult↗

Effect of latanoprost and timolol on the histopathology of the rabbit conjunctiva.

PURPOSE: Long-term medical treatment of glaucoma has an effect on the conjunctiva, possibly affecting the outcome of subsequent filtering surgery. The type and extent of these tissue changes caused by frequently used medications is important. An animal study using rabbits was performed to assess the tissue changes caused by timolol, latanoprost, and a combination of both substances. METHODS: Rabbits were treated with timolol, latanoprost, or a combination of these drugs for 18 months. Conjunctival specimens were examined by light microscopy, quantitative transmission electron microscopy, and immunohistochemistry with antibodies against matrix metalloproteinase (MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-2. RESULTS: By electron microscopy, the area of subepithelial collagen was significantly larger (P: < 0.03; Mann-Whitney test) in timolol-treated eyes (71.6%) than in control (52.7%) and latanoprost-treated eyes (57.7%). An increase of amorphous material was present in timolol-treated eyes (25.6% versus 7.6% in the controls) as well as a smaller area of empty spaces (2.5% versus 39.4% in control eyes). Latanoprost-treated eyes had no significant increase of empty spaces but showed a marked staining for MMP-3 in the conjunctiva. This staining was not present in control or timolol-treated eyes. Morphologically, degenerative changes of fibrocytes were seen in timolol-treated eyes only. CONCLUSIONS: A significant increase of subepithelial collagen density was present in timolol-treated eyes, whereas this finding was not apparent in latanoprost-treated eyes. Latanoprost-treated eyes showed an upregulation of MMP-3, which may be the reason for reduced extracellular matrix accumulation in such eyes. The morphologic feature of increased subepithelial collagen density and extracellular matrix changes may relate to failure of filtering blebs.

Animals↗

Topical fluorouracil. Pharmacokinetics in normal rabbit eyes.

Postoperative subconjunctival fluorouracil injections may be a useful adjunct to standard glaucoma filtering surgery in eyes that are at high risk of failure. Topical administration would be preferable to subconjunctival administration; however, there are no data on the ocular penetration of topically applied fluorouracil. Consequently, we investigated the pharmacokinetics of topically administered fluorouracil labeled with carbon 14 in normal rabbit eyes. One drop (approximately 2.4 mg) of fluorouracil resulted in the following concentrations at 0.5 and six hours, respectively: 17.3 and 0.9 micrograms/g of conjunctiva; 24.3 and 1.3 micrograms/g of cornea; 14.6 and 0.2 micrograms/mL of aqueous; 0.8 and 0.5 microgram/g of lens; 1.1 and 0.3 microgram/g of vitreous; and 0.2 and less than 0.1 microgram/mL of serum. Three drops (approximately 7.2 mg) of fluorouracil resulted in the following concentrations at 0.5 and eight hours, respectively: 589.8 and 1.3 micrograms/g of conjunctiva; 502.9 and 1.8 micrograms/g of cornea; 199.6 and 0.8 micrograms/mL of aqueous; 6.2 and 0.5 micrograms/g of lens; 6.8 and 0.5 micrograms/g of vitreous; and 1.3 and 0.2 microgram/mL of serum. Since a fluorouracil concentration of 0.2 microgram/mL inhibits rabbit conjunctival fibroblast proliferation in cell culture by 50%, these data suggest that topically applied fluorouracil achieves sufficient levels in the ocular compartments and tissues to have potential therapeutic applications.

Administration, Topical↗

Central retinal vein occlusion and malignant glaucoma.

Malignant (ciliary block) glaucoma developed in three patients with primary open angle glaucoma with preexisting central retinal vein occlusion following trabeculectomy. Two of the three patients had 360 degrees open angles prior to surgical trabeculectomy. Although the relationship may be coincidental, we propose that central retinal vein occlusion may be a risk factor for the development of malignant glaucoma following filtering surgery.

Aged↗

Surgical results in iridocorneal endothelial syndrome.

The charts of 83 patients with iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Forty-two eyes of 42 patients had had filtering surgery, 37 of whom had had a trabeculectomy to reduce uncontrolled intraocular pressure. Twenty-four of these trabeculectomy patients required a second surgery, and 8 required a third surgery. The results are presented using a survival analysis. The success rates at one year of follow-up for the first, second, and third trabeculectomies were 64%, 79%, and 63%, respectively. Patients subclassified as having Chandler's syndrome, essential iris atrophy, and Cogan-Reese syndrome responded with approximately the same success rates within the first two years following their first surgery. The success rates for repeated surgeries are comparable with those of initial surgery in patients with primary open angle glaucoma. On the basis of this study, further surgery is recommended despite initial failure in this group of difficult patients.

Endothelium, Corneal↗

Extracapsular cataract extraction using a temporal limbal approach after filtering operations.

We reviewed the charts of 29 patients who underwent extracapsular cataract extraction after filtering surgery. Seven of these patients also had simultaneous implantation of a posterior chamber intraocular lens. All eyes were operated on using a temporal limbal approach. The median postoperative follow-up was 13 months. There was no statistically significant difference between the preoperative and postoperative intraocular pressures, but there tended to be an increase in the number of antiglaucoma medications administered postoperatively. None of these patients, however, required further surgery for intraocular pressure control.

Adult↗

The effect of fluorouracil on the corneal endothelium.

The utility of the antiproliferative agent fluorouracil has been demonstrated recently in glaucoma-filtering surgery and in the management of proliferative vitreoretinopathy after vitrectomy. Because of the potential for contact with the corneal endothelium, its toxicity to the endothelium is an important consideration. The effect of fluorouracil on corneal endothelial integrity in an in vitro animal model was studied. Freshly excised sheep corneal buttons were exposed to increasing concentrations of fluorouracil for four hours and were subsequently evaluated microscopically using vital staining with alizarin red and trypan blue. Exposure to normal saline and chlorhexidine gluconate was used to establish negative- and positive-staining controls. Corneal buttons exposed to normal saline or to 1.0 mg/mL or less of fluorouracil had intact endothelial monolayers that completely excluded trypan blue. Corneal buttons exposed to chlorhexidine gluconate or to 10 mg/mL of fluorouracil, however, had severely or totally disrupted endothelial monolayers in which the remaining cells, if any, all had blue-staining nuclei. These results suggest that the threshold concentration for fluorouracil toxicity to corneal endothelium lies between 1 and 10 mg/mL when exposure time is four hours.

Animals↗

Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C.

Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed.

Animals↗

Transconjunctival application of mitomycin C in combination with laser sclerostomy ab interno: a long-term morphological study of the postoperative healing process.

The precise mechanism whereby mitomycin C enhances IOP reduction in glaucoma filtering surgery still eludes us. Ten rabbits received full-thickness Nd:YAG laser sclerostomy ab interno and adjunctive intraoperative treatment with mitomycin C (MMC) applied topically over the intact conjunctiva (0.5 mg ml-1 for 5 min). A systematic ultrastructural analysis of the fistulas and surrounding tissue was then conducted in conjunction with clinical observations, over the ensuing 10 weeks. In order to investigate also the extent to which MMC impedes fistula occlusion in the absence of percolating aqueous humour, we created non-perforating ('half-thickness') sclerostomies ab interno in three additional rabbits, one with and two without MMC therapy. Transconjunctival MMC application resulted in no serious complications. Eight of the ten full-thickness fistulas remained patent throughout the study, maintaining significant IOP reduction; the other two sclerostomies were compromised by iris incarceration. The MMC-treated, half-thickness canal remained as a tissue-free cul de sac; the two non-treated ones became completely occluded within one week without having recourse to extraocular cell populations. MMC suppressed the migration and proliferation of fibroblasts, macrophages and clump cells from the episclera, sclera, ciliary body and iris root. Repolymerization of heat-damaged collagen was abortive; neosynthesis was not observed. Myofibroblasts were encountered in the vicinity of the sclerostomy canals, and, after the fifth week, these cells were also found to be deployed as a canal-lining layer, delimiting the lumen from the surrounding stroma along most of the fistula length. Towards the external ostium, this layer of myofibroblasts was incomplete or absent. Near the internal ostium, lining cells were derived from the corneal endothelium. The transconjunctival mode of applying MMC appears to be efficient. This antifibrotic drug exerts its inhibitory influence by suppressing not only cell migration and proliferation, but also phagocytic and synthetic activities. However, exposed tissues are not acellular, and amongst the populations present, myofibroblasts are found to dominate the scene. The canal-delimiting cellular lining may play a role in maintaining fistula patency in MMC-treated eyes.

Administration, Topical↗

Growth inhibition of cultured human Tenon's fibroblastic cells by targeting the E2F transcription factor.

The transcription factor E2F regulates the expression of several genes concerned with cell growth. The ability to inhibit transcription by blocking E2F expression has great potential in the treatment of proliferative disorders. The effect of double-stranded phosphorothioate oligonucleotides containing E2F transcription factor cis element, a so called 'decoy' has examined on the growth of cultured human Tenon's fibroblastic cells. Human Tenon's fibroblastic cells were cultured and challenged by E2F decoy coated with the Hemagglutinating virus of Japan (HVJ) cationic liposomes (HVJ-CL). The outcome was evaluated using fluorescence microscopy, RT-PCR and growth assays. HVJ-CL facilitated the transfer of external oligonucleotides to cultured human Tenon's fibroblastic cells. The E2F decoy, transferred by HVJ-CL, inhibited simultaneously the expression of the mRNAs of several cell cycle related genes such as c-myc, cdc2, proliferative cell nuclear antigen, and dehydrofolate reductase. Entry into S phase was also reduced to 42.7% of the positive control by the E2F decoy. The total increase of DNA at four days was reduced to 59.7% of the positive control by 5 microM and 29.9% by 15 microM of E2F decoy. It is concluded that gene therapy using the E2F transcription factor offers a potential therapeutic modality for the treatment of proliferative disorders such as proliferative vitreoretinopathy and fibrosis following filtering surgery.

Carrier Proteins↗