Posterior Lip Sclerectomy Research Articles

Inhibition of Tenon's fibroblast proliferation and enhancement of filtration surgery in rabbits with cytosine arabinoside.

Our purpose was to study the antiproliferative effect of cytosine arabinoside (Ara-C) on rabbit Tenon's fibroblasts and the efficacy of Ara-C as an adjunctive antifibrosis treatment for glaucoma filtration surgery in the rabbit eye. Rabbit Tenon's fibroblasts were exposed to 1 microg/ml of Ara-C for various time intervals, then cell number and viability was assessed at different time points. Following posterior lip sclerectomy, rabbit eyes were treated with 10 mg subconjunctival Ara-C daily for 7 days, then every other day for 7 days. Rabbit fibroblasts exposed to 1 microg/ml Ara-C for 1 hour showed no significant decrease in cell number compared with control. Continuous or 24-hour incubation of fibroblasts with Ara-C was lethal to the cells. Exposure of cells to Ara-C for 3-, 6-, and 9-hour intervals caused significant reduction of cell proliferation. Pulsed treatment of cells with 6 hour exposure to 1 microg/ml Ara-C every 3 days caused prolonged suppression of cell proliferation. Following posterior lip sclerectomy in rabbits, topical instillation of Ara-C drops at varying concentrations and dosing intervals did not cause any significant lowering of intraocular pressure compared with control eyes, although bleb survival was prolonged in eyes treated with Ara-C (P < 0.01). In rabbit eyes treated postoperatively with subconjunctival injections of 10 mg Ara-C every other day for two weeks, the mean intraocular pressure was significantly decreased and the bleb survival time was significantly prolonged (P < 0.0067) compared with control eyes. In conclusion, Ara-C inhibits rabbit Tenon's fibroblast proliferation in vitro. Postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit.

New patterns of infecting organisms in late bleb-related endophthalmitis: a ten year review.

To report the risk factors, causative organisms and visual outcomes in patients with late-onset bleb-related endophthalmitis. Medical records of all patients with the clinical diagnosis of late-onset bleb-related endophthalmitis undergoing vitreous aspirates for culture at our institution from January 1987 to July 1996 were reviewed. Late-onset bleb-related endophthalmitis was defined as conjunctival injection, bleb purulence and intraocular inflammation developing at least 1 month following filtering surgery. Forty-nine cases of bleb-related endophthalmitis developed in 42 patients (23 men, 19 women). Mean patient age was 62.1 +/- 19.3 years (range 5-94 years). Thirty-nine patients underwent prior filtering surgery (superior trabeculectomy, 24 eyes; inferior trabeculectomy, 10 eyes; combined superior trabeculectomy/cataract extraction, 4 eyes; posterior lip sclerectomy, 1 eye) and 3 had inadvertent blebs following cataract extraction. Endophthalmitis developed an average of 25.4 +/- 23.5 months (range 1-96 months) post-operatively. Antifibrosis agents were used in 25 of 39 eyes undergoing filtering surgery (mitomycin C, 13 eyes; 5-fluorouracil, 12 eyes). Bleb leaks were documented in a total of 32 of 49 (65%) cases either before or at the time of endophthalmitis diagnosis. Vitreous cultures were positive in 42 of 49 (86%) cases. The most frequently cultured organisms were Staphylococcus aureus (13), Staphylococcus epidermidis (12), Streptococcus species (8) and Haemophilus influenzae (2). A final visual acuity of 20/400 or better was achieved in 32 of 49 (65%) cases. Staphylococcal species were the most frequently cultured organisms in this series and may be associated with better visual outcomes. Although a causal relationship cannot be established, these results suggest a strong association between bleb leaks and endophthalmitis.

The Effect of Paclitaxel Powder on Glaucoma Filtration Surgery in Rabbits

The authors determine if the intraoperative placement of paclitaxel powder in the subconjunctival space improves the outcome of glaucoma filtration surgery in rabbits. A posterior lip sclerectomy was performed in the right eye of 24 New Zealand white rabbits. Before the conjunctiva was fully sutured, 8 mg of mannitol powder alone, or 8 mg of mannitol powder containing either 10 micrograms or 250 micrograms of paclitaxel, was placed in the subconjunctival space of six eyes each in masked fashion. An additional six animals were treated with episcleral application of a sponge soaked in a solution of 0.5 mg/ml of mitomycin C (MMC) for 5 minutes before the sclerectomy was performed. Intraocular pressure and bleb size were measured until the operation had failed or until the 7 weeks of observation had concluded. Both paclitaxel powder and MMC solution improved the outcome of filtration surgery in this model as measured by magnitude of intraocular pressure (IOP) lowering and duration of surgical success. No toxic effect of either drug was observed, although endophthalmitis was observed in eight animals followed for more than 3 weeks. The introduction of paclitaxel into the subconjunctival space at the conclusion of filtration surgery has an effect comparable to intraoperative MMC.

Gonioscopic laser sclerostomy versus filtration surgery in a rabbit model.

In a prospective and randomised study, we compared the course of pulsed dye laser ab interno sclerostomy with the course of posterior lip sclerectomy in 25 rabbits. One eye of each rabbit was randomly selected to be treated with laser; the fellow eye underwent posterior lip sclerectomy. Intraocular pressure (IOP) determinations and slit lamp examinations were recorded pre-operatively, then every other day for 3 weeks on 21 of the rabbits. Histological examination was performed on the eyes of 3 randomly selected rabbits that were killed 72 hours post-operatively. Laser sclerostomy resulted in an average maximal drop in IOP of 9.5 mmHg on post-operative day 1, and posterior lip sclerectomy resulted in a similar drop of 10.5 mmHg (p = 0.43, t-test). By life-table analysis, 88% of eyes returned to within 2 mmHg of pre-operative IOP values within 7 days following either laser internal sclerostomy or posterior lip sclerectomy. There was no significant difference between laser internal sclerostomy and posterior lip sclerectomy eyes with respect to the number of days needed to return to within 2 mmHg of preoperative IOP values (p = 0.26, sign test of the life-table analysis). Pulsed dye laser internal sclerostomy appears to be as effective as posterior lip sclerectomy in lowering IOP in the rabbit model.

The Use of Bioerodible Polymers and Daunorubicin in Glaucoma Filtration Surgery

Purpose: Glaucoma filtering surgery usually fails from postoperative fibroblast proliferation, collagen deposition, and subsequent sclerostomy or bleb scarring. Daunorubicin inhibits fibroblast proliferation in vivo and in vitro. The authors studied the effect of a sustained subconjunctival release of daunorubicin by way of a bioerodible polymer on the success of glaucoma filtration surgery in a rabbit model.Methods: Daunorubicin was incorporated into the copolymer by compression molding. The resultant implant measured 3.0 mm in diameter, 1.0 mm in thickness, and 8.0 mg in weight. A posterior lip sclerectomy was performed in both eyes of 23 rabbits by the same surgeon. One eye was randomized to receive the disc with daunorubicin, whereas the fellow eye received a blank disk as a control. The appropriate polymer disk then was placed on the scleral surface immediately posterior to the sclerostomy site and the conjunctiva was closed. Intraocular pressures and slit-lamp biomicroscopy were recorded preoperatively, then every other day after surgery for 31 days. Intraocular pressure, bleb survival, and complications were evaluated.Results: The decrease in intraocular pressure from baseline was significantly greater in the daunorubicin eyes than in the control eyes during postoperative days 5 through 25. Bleb survival was significantly longer in the daunorubicin eyes than in the control eyes (bleb failure in 91% of control eyes versus 22% of treatment eyes by day 13). There were no statistically significant differences between the daunorubicin-treated and control eyes regarding corneal clouding, lens clarity, cataract formation, or conjunctival injection. However, conjunctival erosions occurred in four daunorubicin-treated eyes. Histopathologic examination was performed 2 weeks after surgery on the eyes of three randomly selected rabbits.Conclusion: Daunorubicin in a bioerodible delivery system may potentially be a useful adjunct to glaucoma filtering surgery and requires further evaluation.

Safety and efficacy of combined phakoemulsification, posterior chamber lens implant and posterior lip sclerectomy.

Safety and efficacy of combined phakoemulsification, posterior chamber lens implant and posterior lip sclerectomy.

Extracapsular Cataract Extraction and Posterior-Lip Sclerectomy With Viscoelastic

A review of 15 cases suggests that posterior-lip sclerectomy can be performed safely with extracapsular cataract extraction (ECCE) and posterior chamber lens implantation. The anterior chamber was filled with viscoelastic at the end of each procedure; no case required reoperation for shallow chamber or hypotony. The mean intraocular pressure after 1 year was 12.1 mm Hg. The astigmatism induced by the triple procedure did not differ significantly from that caused by ECCE alone during the initial 2 postoperative years. A new mathematical model that describes the change over time of postoperative astigmatism associated with these procedures is described.

Enhancement of filtration surgery with cytosine arabinoside and reversal of toxicity with 2'-deoxycytidine.

Antifibrosis agents have improved the success of glaucoma filtration surgery, although undesired side effects are not readily reversible and may present a major limitation in the use of these agents. Our purpose was to study the efficacy of cytosine arabinoside (Ara-C) as an adjunctive antimetabolite in glaucoma surgery in the rabbit, and reversal of toxicity due to this agent with the competitive inhibitor 2'-deoxycytidine. Posterior lip sclerectomy was performed in rabbit eyes treated with 15 mg subconjunctival Ara-C daily for 7 d then every other day for 7 d. Mean intraocular pressure was lower in eyes treated with Ara-C compared with controls at all time points following filtration surgery. On the 10th postoperative day, the mean intraocular pressure of control eyes (25.0 +/- 1.9 mm Hg) had returned to baseline levels, whereas the intraocular pressure of eyes treated with Ara-C was significantly lower (16.0 +/- 1.7 mm Hg) (P < 0.001). Bleb survival was also prolonged in the Ara-C-treated eyes. The major ocular side effect of Ara-C was corneal toxicity, with epithelial defects in 40% of eyes after 8 daily injections of 15 mg Ara-C. Reversal of toxicity was enhanced with 2'-deoxycytidine, with complete resolution of epithelial toxicity after 6.5 +/- 1.7 d following daily topical 10% 2'-deoxycytidine compared with 12.7 +/- 0.58 for control (P < 0.002). These results demonstrate that postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit. Recovery from corneal epithelial toxicity due to Ara-C is markedly enhanced with the competitive inhibitor 2'-deoxycytidine.

Pharmacokinetics of Etoposide Delivery by a Bioerodible Drug Carrier Implanted at Glaucoma Surgery

Pharmacological modulation of wound healing after glaucoma filtration surgery is of great clinical interest, but there are only limited data available on drug pharmacokinetics following glaucoma filtration surgery. Therefore we have studied the in vivo release and tissue distribution of etoposide (VP-16) delivered subconjunctivally by a bioerodible drug-carrier during filtration surgery in rabbits. Disks composed of the polyanhydride 1,3-bis(p-carboxyphenoxy) propane and sebacic acid (PCPP:SA) in a weight ratio of 25:75 and containing 1 mg of 3H-etoposide were placed subconjunctivally during posterior lip sclerectomy in one eye of albino rabbits. Animals were euthanized at various times after surgery and etoposide concentrations in fluids and tissues were determined using liquid scintillation counting. Release of etoposide from the implant was nearly linear over time, at 30 ug/day, except for a burst between days 6 and 7. By the twelfth postoperative day, 92% of the etoposide had been released. Steady state levels averaged 89 ng/mg in the conjunctiva and sclera, 195 ng/ml in the vitreous, and 29 ng/ml in serum. Drug levels in the aqueous humor, other ocular tissues, and in the contralateral eye were negligible. The concentration of etoposide delivered by a polyanhydride controlled release device on the ocular surface is sufficient to reduce fibroblast proliferation for at least 12 days after filtration surgery.

193-nm excimer laser sclerostomy using a modified open mask delivery system in rhesus monkeys with experimental glaucoma.

Excimer laser sclerostomy is a new glaucoma filtration procedure in which the argon fluoride excimer laser at 193 nm is delivered ab externo through a modified open mask system incorporating an en-face air jet to dry the target area and preserve hemostasis during ablation and a conjunctival plication mechanism, which allows the conjunctival and scleral wounds created by through-and-through ablation to separate once the mask is removed. No preparatory dissection of the conjunctiva is required. Five 200-microns and five 500-microns sclerostomies were formed by ablation at a pulse repetition rate of 20 Hz and a fluence per pulse of 400 mJ/cm2 in fellow eyes of five rhesus monkeys with experimental glaucoma. Overall, seven of the ten eyes attained a functional result, with intraocular pressures remaining below 21 mmHg for 6 +/- 1 days and rising to the pre-operative level after 10 +/- 3 days without adjunctive antifibroblast medication. The duration of filtration for 200-microns and 500-microns sclerostomies was similar, and parallels that previously observed for posterior lip sclerectomy in the same animal model. The three eyes with no functional result all had incorrectly positioned sclerostomies. Choroidal detachment and significant shallowing of the anterior chamber did not occur. Excimer laser sclerostomy appears to be a viable technique for filtration, provided that mask placement is accurate.

Effects of Cy to sine Arabino side-Impregnated Bioerodible Polymers on Glaucoma Filtration Surgery in Rabbits

A prospective, randomized double-masked placebo-controlled study was performed to determine the effects of a bioerodible polymer containing cytosine arabinoside (Ara-C) on the success of full thickness filtration surgery in 21 rabbits. The polymer was a polyanhydride composed of bis(pcarboxyphenoxy) propane and sebacic acid. The polymer and Ara-C (1 mg by weight) were combined and compressed into discs 3-mm and 1-mm thick. Control polymers contained no Ara-C. Posterior lip sclerectomy surgery was performed bilaterally, with one eye randomly receiving the polymer with the Ara-C and the fellow eye receiving the control polymer. All eyes were examined on the first postoperative day and every other day thereafter. Intraocular pressures (IOPs) were found to be significantly lower (p < 0.04) in the experimental eyes during the 5th through the 15th postoperative day, with the mean difference ranging from 3.5 to 6.0 mm Hg. The median number (+/-SE) of days until failure of the filters was 10.5 (+/-0.66) days in the control group and 15.2 (+/-1.94) days in the experimental group, the difference being statistically significant. There were no significant differences between the groups with regard to conjunctival injection, corneal epithelial defects, anterior chamber inflammation, lens changes, or intraoperative or postoperative complications. This study suggests that polymer drug delivery of Ara-C may be a safe and efficacious adjunct in temporarily increasing the success rate of glaucoma filtering surgery in a rabbit model.

Effects of sodium hyaluronate on filtration bleb in rabbits.

Sodium hyaluronate can be used during a trabeculectomy to prevent early postoperative hypotony and shallow anterior chamber. To determine its long-term effect on the outcome of filtration surgery, fifteen rabbits underwent a posterior-lip sclerectomy in both eyes. Into their right eyes 0.2ml sodium hyaluronate, and into left eyes 0.2ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. There was no statistically significant difference in longevity of the filtration bleb.

Advances in laser sclerectomy.

LAUCOMA SURGERY has undergone a G continuous process of evolution. There has been significant impetus to search for more successful surgical techniques because of the risk of surgical failure after conventional filtration procedures. These include trephination, thermal sclerostomy, posterior lip sclerectomy, and trabeculectomy. Failure to control the intraocular pressure may occur because of preoperative characteristics, such as aphakia,lP2 young age,3 and race.4 African Americans respond less well to filtration surgery. Previous filter failures decrease chances of success following subsequent filtration attempt^.^ Perioperative factors contributing to failure include incarceration of iris, vitreous, or ciliary processes into the internal ostium.6 Blood or fibrin may also occlude the ostium. Excessive conjunctival and episcleral inflammation and hemorrhage, tissue manipulation, subconjunctival fibrosis, tight scleral sutures, and uveitis can lead to closure of the sclerectomy opening and bleb Trabeculectomy is a guarded filtration procedure distinct from the other available procedures. Postoperative complications associated with fullthickness surgery are higher, leading to trabeculectomy as the preferred procedure of most surgeon^.^ Patients who have had repeated surgical failures following conventional filtration procedures and patients with neovascular glaucoma that does not respond to routine glaucoma surgery may do better with drainage shunts and implants.lOJ1 The recognition of the importance of wound healing as a cause of surgical failure has led to the widespread use of wound modulating agents, such as 5-flU01-0uracil, and recently mitomycin-C, with improved suc~ess.~~J~

The Use of Tissue Plasminogen Activator in Experimental Filtration Surgery

Tissue plasminogen activator (tPA), a clot-specific fibrinolytic agent, was used as an adjunct to filtration surgery in Dutch belted rabbits to determine its effects on the outcome of filtration surgery. Thirty-eight animals that underwent a standardized posterior-lip sclerectomy in both eyes were divided into five postoperative protocol groups. In masked fashion, experimental eyes received 25 micrograms of tPA in 100 microL of diluent. Fellow eyes received 100 microL of diluent and served as controls. Group 1 received daily subconjunctival tPA. Group 2 received intracameral, followed by daily subconjunctival, tPA. Groups 3, 4, and 5 received intracameral tPA on postoperative days 1 and 2;2 and 3; and 3, 4, and 5, respectively. Intraocular pressure (IOP), quality of bleb, number of days to bleb failure, and incidence of intraocular bleeding were determined in each group. No significant tPA effect was seen in groups 1 or 2. In groups 3, 4, and 5, the tPA-treated eyes demonstrated marked reduction of IOP and improvement in the quality of the blebs lasting between 6 to 24 hours.

Effects of aqueous humor on filtering bleb in rabbits.

Preoperative aqueous humor, known to inhibit the growth of fibroblasts in tissue culture assay, was used as an adjunct to filtering surgery in rabbits to determine its effect in vivo on the outcome of filtering surgery. Fifteen rabbits underwent a posterior-lip sclerectomy in both eyes. In experimental eyes 1.4 ml preoperative aqueous humor and in fellow eyes 1.4 ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. In this animal experiment, although there was no statistical significance or late postoperative effect, the rabbit eyes refilled with preoperative aqueous humor intracamerally just after filtering surgery, had a larger bleb and less fibroconnective tissue on the bleb than the control eyes in the early postoperative period.

Effect of gamma-interferon on fibroblast proliferation and collagen synthesis after glaucoma filtering surgery in white rabbits

Failure of a glaucoma filtering operation mainly results from scarring at the filtering wound, and postoperative proliferation and migration of fibroblasts play an important role histologically in the formation of scar tissue. As an inhibitory agent for fibroblast proliferation, gamma-interferon has been introduced, and the application of gamma-interferon following filtering surgery is now being made on a trial basis. We studied the effect of gamma-interferon histologically on the fibroblast proliferation and collagen synthesis occurring at the filtering site by comparing the effect of gamma-interferon on the experimental group with that of 5-fluorouracil on the control group, using 10 rabbits (20 eyes) after posterior lip sclerectomy. Both groups showed similar flat and diffused bleb grossly and also showed a similar inhibitory effect on fibroblast proliferation and collagen fiber synthesis histologically. Our findings seem to justify the clinical use of gamma-interferon. Further studies on adequate dosage, method of administration, and local and systemic complications would be desired.

Effects of Topical Glaucoma Drugs on Fistuliezed Rabbit Conjunctiva

Conjunctival fibroblastic proliferation with contracting scar formation has been implicated as a possible cause of glaucoma filtering surgery failure. The effects of glaucoma medications on bulbar conjunctiva were evaluated in both eyes of 20 pigmented rabbits, with 5 rabbits per group each receiving singular topically applied daily doses of either 0.5% timolol, 1% epinephrine, 4% pilocarpine, or artificial tears in a masked fashion for 4 months. Posterior lip sclerectomies were performed in 16 rabbits-4 from each treatment group. The remaining four rabbits served as nonsurgical controls. Four additional rabbits, which had not received eye drops, were included as a nonmedicated control group, with one rabbit serving as a nonsurgical control. Immunostaining was performed to identify the presence of myofibroblasts in fistulized conjunctiva. Treated surgical eyes, regardless of medication, had higher myofibroblastic cell proliferation than treated nonsurgical eyes. Among fistulized eyes, all medications increased cell proliferation, with pilocarpine eliciting the most dramatic increase compared with all other groups.

Postoperative Intraocular Pressure Rise in Open-angle Glaucoma Patients after Cataract or Combined Cataract-filtration Surgery

Postoperative intraocular pressure (10P) was measured in patients with open-angle glaucoma undergoing extracapsular cataract extraction with a posterior chamber lens implant (ECCE-PC IOL). Patients considered to be under adequate medical glaucoma control had cataract surgery alone or combined with a posterior lip sclerectomy. Patients with medically uncontrolled glaucoma had cataract surgery combined with either a posterior lip sclerectomy or a trabeculectomy. Cataract surgery alone (n = 26) was associated with a significantly (P < 0.001) increased IOP on postoperative day 1: preoperative IOP, 18.9 ± 3.6 mmHg; postoperative IOP, 34.2 ± 12 mmHg. An IOP rise of 10 mmHg or more occurred in 69% of the eyes, whereas 77% of the eyes had an absolute IOP over 25 mmHg. Eyes undergoing combined surgery (n = 42) had a preoperative IOP of 21.3 ± 4.8 mmHg. On postoperative day 1, the mean IOP was 14.9 ± 12.0 mmHg. An IOP rise of 10 mmHg or more was observed in 14%, and an IOP over 25 mmHg in 21 % of combined surgery eyes. Cataract surgery in eyes with open-angle glaucoma requires careful monitoring and therapy for early postoperative increases in IOP. Combined surgery reduces the frequency and magnitude of, but does not eliminate, this complication.

Failed Laser Trabeculoplasty Requiring Surgery in Open-Angle Glaucoma

Argon laser trabeculoplasty (ALT) has been successful in controlling open-angle glaucoma, but a significant number of patients still require filtration surgery. Concern that post-laser inflammatory changes or alterations of structural anatomy with damage to the trabecular meshwork may adversely affect the outcome of filtration surgery prompted a retrospective review of 87 consecutive eyes with open-angle glaucoma that required filtration surgery following failed ALT. The follow-up period was at least 6 months, with a mean of 18 months (6 to 38 months). Posterior lip sclerectomy was chosen for 69 eyes and trabeculectomy for 18 eyes. The overall success rate of filtration surgery during the follow-up period was 92%. There was no recognized difference in the response to filtration surgery following ALT.

Filtration Surgery in Black Patients: Early Results in a West Indian Population

We reviewed the early results of 80 filtration procedures when used as the initial surgical treatment in a Saint Lucian West Indian black population with primary open angle glaucoma. Two techniques were used: trabeculectomy under a scleral flap with fornix-based conjunctival flap (Group 1) and full thickness posterior lip sclerectomy with limbal-based conjunctival flap (Group 2). Postoperatively, with an average follow-up of six months, Group 2 had significantly lower intraocular pressures, reduced glaucoma medication requirements, and increased cystic bleb formation. Vision did not differ significantly between the two groups postoperatively, although two Group 1 patients developed progressive glaucomatous visual loss. Complications were slightly more frequent in Group 2. The results of this study suggest that a full thickness sclerectomy technique merits consideration as the initial filtration procedure of choice in West Indian blacks with advanced open angle glaucoma.