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Glaucoma and Peters' anomaly. A clinicopathologic case report.

A 26-year-old black woman with Peters' anomaly who had been followed since early childhood developed an open-angle form of glaucoma, which required filtering surgery. Light and electron microscope studies of the trabeculectomy specimen, which was obtained by en bloc resection of the trabecular meshwork and iridectomy specimen, revealed that the structures of the anterior-chamber angle were grossly normal aside from evidence of premature aging on the basis of abundant broad-banded collagen fibers in the trabecular lamellae.

Adult↗

Uncontrolled primary angle closure glaucoma: results of early intercapsular cataract extraction and posterior chamber lens implantation.

In this study we retrospectively evaluated the effect of intercapsular or extracapsular cataract extraction and posterior chamber lens implantation in 67 eyes of 57 patients with different types of primary angle closure glaucoma (PACG) in combination with cataract. We subdivided this patient population into three groups, based on the preoperative methods of intraocular pressure (IOP) control. The best results were obtained in patients with acute PACG (55% IOP reduction) and in patients with uncontrolled PACG (44% IOP reduction). In the other PACG groups an IOP reduction of between 20 and 33% was achieved. A long-term postoperative IOP of less than 21 mmHg was established in 63 eyes or 94%. In 91% the glaucoma medication was reduced, 65% of all eyes needed no glaucoma medication postoperatively. We conclude that an intercapsular cataract extraction with PC-IOL implantation should be considered in both controlled and uncontrolled PACG in patients with cataract, instead of filtering surgery or combined procedures. Even in eyes with relatively good visual acuity, cataract extraction might be considered as a means of achieving glaucoma control.

Acute Disease↗

Growth inhibition of human Tenon's capsule fibroblasts and rabbit dermal fibroblasts with non-carcinogenic N-alkylated anthracyclines.

Bleb fibrosis after glaucoma filtering surgery and proliferative vitreoretinopathy after retinal detachment surgery are complications caused by proliferation of fibroblasts or fibroblastlike cells. The anthracycline daunomycin (DNM) has been used for treatment of those proliferative processes in humans. However, complications such as conjunctival necrosis and corneal or scleral ulcerations have been reported after administration of DNM to glaucoma patients. Intravitreal administration of DNM in rabbit eyes resulted in morphological and functional retinal damage. DNM also has the undesired general effect of carcinogenicity. N-Alkylation of the aminosugar moiety of DNM results in reduction or loss of carcinogenicity. We evaluated the inhibitory effect of the new non-carcinogenic N-alkylated analogues aclacinomycin A (ACA), N,N-dimethyladriamycin (AD280), and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143) on the growth of cultured human Tenon's capsule fibroblasts and rabbit dermal fibroblasts. Using DNM as a positive control, we conducted proliferation assays that demonstrated that ACA and AD280 inhibited fibroblast growth as effectively as DNM. AD143 was less efficacious. The magnitude of cellular growth inhibition was concentration dependent for all drugs tested. Extension of exposure times resulted in increased rates of cell death. Our in vitro studies suggest that further evaluation of ACA and AD280 should be carried out in animal models of ocular proliferative disorders.

Animals↗

Effect of lysyl hydroxylase inhibitor, minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts.

BACKGROUND: Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. METHODS: Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. RESULTS: Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. CONCLUSIONS: The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.

Animals↗

Daunorubicin versus 5-fluoro-uracil in surgical treatment of primary open angle glaucoma: a prospective study.

In a prospective randomized study, we compare the results at 20 months of 5 Fluoro-Uracil and Daunorubicin filtering surgery in two groups of 25 patients with primary open-angle glaucoma. For the first group of 14 eyes, 10 injections of 5FU are done and only one subconjunctival preoperative injection of Daunorubicin in the second group of 13 eyes. 5FU group consists of 13 patients: 9 males, 4 females. The mean age is 52.3 +/- 18.4 years. The mean follow-up is 6.9 +/- 7 months. Daunorubicin group consists of 12 patients: 9 males, 3 females. The mean age is 50.2 +/- 21.4 years. The mean follow-up is 7.3 +/- 7 months. By Kaplan-Meier method, the probability success rate is 79 per 100 with 5FU and 68 per 100 with Daunorubicin. After 5FU procedure, the most disturbing complication is related to the decrease in IOP during the first postoperative days: flat anterior chamber (9 eyes) (7 eyes after Daunorubicin), choroïdal detachment (6 eyes) (2 eyes after Daunorubicin), cataract (3 eyes in the two groups). After Daunorubicin, corneal complications are less frequent: corneal ulcer (2 eyes) (3 eyes after 5FU), corneal dystrophy (1 eye in the two groups). Transient chemosis and local palpebral oedema are constant after Daunorubicin. We compared the IOP reduction rate and visual function loss in the two groups.

Aged↗

Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts.

Rabbits undergoing full thickness glaucoma filtering surgery were exposed to one of 4 treatments. Group 1 received intraoperative distilled water, group 2 received intraoperative mitomycin-c 0.2 mg/ml for 5 minutes, group 3 received 5 post operative injections of 5-Fluorouracil (5-FU) 5 mg in 0.1 ml, and group 4 received intraoperative 5-FU 50 mg/ml followed by 5 post operative injections of 5-FU. 30 days after the operation tissue biopsies were taken from the subconjunctival and scleral tissue at the treated area and 90 and 180 degrees from the treated area. The biopsies were then placed in tissue culture media and the outgrowths quantitated. The fibroblast outgrowths from all areas did not differ significantly from each other except for the outgrowths from the areas directly treated with mitomycin 0.2 mg/ml which were significantly smaller. In addition then cells were morphologically abnormal although there were foci of normal cells which appeared to be growing from localised areas in the tissue biopsies. The outgrowths from the areas 90 and 180 degrees from the treated area were normal. Intraoperative treatments with mitomycin-c result in long term inhibition of fibroblast proliferation limited to the treated area, when compared with intraoperative and postoperative treatment with 5-FU. Failure of filtration surgery in eyes treated with intraoperative mitomycin may in part be due to unaffected cells reproliferating.

Animals↗

Long-term effects of glaucoma therapy with 4% pilocarpine gel on corneal clarity and endothelial cell density.

Corneal thickness measurements and endothelial cell counts were carried out in 34 patients undergoing treatment for glaucoma with 4% pilocarpine gel between 18 to 78 months after initiation of therapy. The corneal thickness and endothelial cell population were found to be within normal limits in all cases except two, one patient with increased corneal thickness who had recently undergone cataract and glaucoma filtering surgery and another patient with decreased cell count who had an old endothelial scar sustained prior to pilocarpine gel therapy. There was a very close correlation for both of these parameters noticed in patients treated with pilocarpine gel and in age-matched control group of patients with glaucoma. The present study has shown that there are no adverse corneal effects with pilocarpine gel therapy.

Adolescent↗

Interferon-alpha 2b inhibits proliferation of human Tenon's capsule fibroblasts.

To evaluate the potential of interferon-alpha 2b (IFN-alpha) as an antifibrotic treatment after glaucoma filtering surgery, we studied its ability to inhibit mitogen-induced proliferation of human Tenon's capsule fibroblasts in vitro, as shown by [3H]-thymidine incorporation. IFN-alpha inhibited fetal calf serum-induced proliferation in a dose-dependent manner in concentrations ranging from 10 to 10,000 IU/ml (P < 0.001). Inhibition was also found when IFN-alpha was added prior to the mitogen (P = 0.001); this inhibitory effect lasted at least 3 days. We suggest that IFN-alpha deserves further evaluation as a possible agent for the control of ocular fibrosis.

Cell Division↗

Results of a filtering procedure in low tension glaucoma.

Twenty-six eyes of twenty patients with established low tension glaucoma, who had either a 'double flap' Scheie filtering operation or a trabeculectomy, were followed over a period ranging from one to ten years, with a median of three years. These 26 eyes include two second eyes that served as a contralateral control eye until the visual field deteriorated. All 26 eyes showed progression of visual field defects preoperatively, while postoperatively only 2 eyes showed further progression. Of the 16 nonoperated contralateral eyes, 7 showed progression of visual field defects over the same follow-up period. Two of these 7 eyes had to be operated during the study-period. The difference in progression between the operated and the non-operated eyes was significant (P less than 0.01). The filtering procedure provided a reduction in IOP of 20% or more in 21 of 26 eyes. There was a significant difference in the mean intraocular pressure (IOP) between the operated and the non-operated contralateral eye of 6.8 mmHg (37%) at one year postoperatively. The diurnal variation decreased highly significantly from 4.3 to 2.1 mmHg (P less than 0.001). It is concluded that filtering surgery in low tension glaucoma may result not only in a significant lowering of IOP, but is also effective in slowing further deterioration of the visual fields.

Adult↗

Long-term results of 5-fluorouracil trabeculectomy for primary open-angle glaucoma.

The effect of 5-fluorouracil (5-FU) subconjunctival injection on the bleb formation and intraocular pressure (IOP) following trabeculectomy was studied in 27 primary open-angle glaucoma patients (33 eyes) who had never been operated upon (25 eyes) or had undergone single trabeculectomy that failed to reduce IOP (8 eyes). The results were analyzed by means of life table analysis and compared with those of 65 primary open-angle glaucoma eyes that had undergone trabeculectomy without postoperative administration of 5-FU as the first or the second filtering surgery. The surgical techniques and postoperative care were virtually identical between the eyes treated with 5-FU and the eyes that had undergone trabeculectomy without 5-FU. At the end of 28-month follow-up, the success probability was 74.8% without any postoperative antiglaucoma medication, and 100% with antiglaucoma medication. Whereas, the success probability with postoperative antiglaucoma medication was as low as 60.8% for the first, and 51.5% for the second trabeculectomy without 5-FU at the 24-month follow-up. Postoperative, subconjunctival injection of 5-FU appears to improve the prognosis following trabeculectomy in primary open-angle glaucoma patients.

Adult↗

[Follow-up of trabeculectomy. Complications and therapeutic consequences].

BACKGROUND: Intensive follow-up after trabeculectomy is important for long-term success. In the postoperative period, complications must be detected early in order to initiate adequate therapeutic measures. PATIENTS AND METHODS: In a retrospective study 113 eyes from 113 consecutive patients were followed-up for a period of 6 months after trabeculectomy with regard to postoperative complications and therapeutic decisions (invasive and conservative). Criteria of success were defined as an intraocular pressure (IOP) < 21 mmHg without antiglaucomatous treatment as well as an IOP reduction > 20% compared to the preoperatively treated IOP. RESULTS: Most of the postoperative complications occurred within the first 3 weeks: scarring of the filtering bleb (47.6%), choroidal detachment (18.6%), shallowing of the anterior chamber (8%), fibrinous reaction (5.3%), overfiltration (4.4%), reduced flow under the scleral flap (4.4%), corneal dellen (3.5%), prolapse of the iris (3.5%), external fistulation (2.7%), increase of the IOP due to steroids (1.8%), detachment of the ciliary body (1.8%) and malignant glaucoma (0.9%). In the postoperative period, 45.1% of the eyes needed further interventions such as 5-fluorouracil (5-FU) injections (28.3%), needling and 5-FU-injections (14.2%), laser suturolysis (6.2%). Repositioning of the iris, YAG-laser iridotomy, laser treatment of the filtering bleb, autologous blood injection and cyclocryoapplication were needed only in rare cases and 36.3% received other conservative treatment (i.e. modification of topical steroids, increase of cycloplegic treatment). After 6 months the success rate without antiglaucoma medication was 88.5%. CONCLUSIONS: An intensive follow-up after trabeculectomy is mandatory to avoid postoperative failure. In about half of the patients postoperative additional therapeutic measures became necessary, particularly if scarring of the filtering bleb occurred. Paying attention to these factors yields in a high success rate after filtering surgery.

Adult↗

Laser-grid trabeculectomy in rabbits: an experimental in-vivo study.

BACKGROUND: Laser-grid trabeculectomy (TE) is a modification of micro-TE designed to enhance the intra- and postoperative safety of filtering surgery by creating several small oval fistulas (max. diameter <200 microm) beneath a scleral flap without peripheral iridectomy. METHODS: After dissecting the conjunctiva and a conventional scleral flap, 10 small perforating fistulas were created in five pigmented rabbits in the region of the gray-white border using an erbium:YAG laser with a beveled side-firing 200 microm endoprobe; conventional TE with iridectomy was performed in another five animals. Anterior chamber inspection and IOP measurements of both eyes were conducted on days 1, 4, and 14 after operation. After the last inspection eyes were saved for morphological analysis. RESULTS: Both procedures (laser-grid and conventional TE) led to a reduction of intraocular pressure in the treated eye compared to the control eye. Differences between the outcomes for the two procedures were not statistically significant. Morphology of the eyes treated by laser-grid TE revealed dense scarring of perforations around the center of the ligamenta pectinata and loose tissue refilling of the more peripheral openings. CONCLUSIONS: The functional outcome of laser-grid TE in rabbits was similar to that of conventional TE in the short term. Histological examination of microperforations in the area of the trabecular meshwork after 2 weeks indicated that tissue repair was less pronounced than in the more anterior perforations. This morphologic finding may be of importance for non-penetrating glaucoma surgery.

Animals↗

Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts.

BACKGROUND: The combined effect of electric pulses (EP) and antiproliferative agents on the proliferation of rabbit Tenon's capsule fibroblasts was investigated. METHODS: Rabbit Tenon's capsule fibroblasts were cultured. Some of these cells were exposed to various intensities of EP alone (500-2500 V/cm). Other cells were then exposed for 30 min to an antiproliferative agent: bleomycin (BLM; 0.0005-50 mumol/l), mitomycin C (MMC; 0.0005-50 mumol/l), 5-fluorouracil (5-FU; 0.05-5000 mumol/l), or streptomycin (SM; 0.0005-50 mumol/l) with or without EP (2000 V/cm, 99 mus, eight pulses). Cell proliferation was assessed by cell counting on day 3 and by a 3H-thymidine uptake assay. DNA fragmentation was assessed by flow-cytometric analysis and agarose gel electrophoresis. RESULTS: A significant reduction in the cell number was observed only at 2500 V/cm (P < 0.05). BLM, MMC and 5-FU treatment inhibited cell proliferation in a dose-dependent manner either with or without EP (ID50: BLM alone, 0.029 mumol/l; BLM and EP, 0.00022 mumol/l; MMC alone, 41.6 mumol/l; MMC and EP, 27.5 mumol/l; 5-FU alone, 1045 mumol/l; 5-FU and EP, 690.2 mumol/l; P < 0.05). EP treatment induced an inhibitory effect of BLM on cell proliferation which was 100 times more prominent than BLM alone (0.0005 mumol/l of BLM alone 103.4 +/- 4.4%, 0.0005 mumol/l of BLM and EP 26.0 +/- 4.4%; P = 0.021). BLM treatment with EP also augmented the apoptotic-like DNA fragmentation in both a flow-cytometric DNA histogram and agarose gel-electrophoresis. CONCLUSION: EP treatment enhanced the inhibitory effect of BLM on the cell proliferation of Tenon's capsule fibroblasts of rabbits. The combination of electric pulses and antiproliferative drug treatments may therefore reduce the necessary dose of antiproliferative agents in filtering surgery.

Animals↗

Conditions for balance between lower normal pressure control and hypotony in mitomycin trabeculectomy.

BACKGROUND: Striving for low to ultra-low postoperative intraocular pressure (IOP) through filtering surgery usually increases the incidence of prolonged hypotony. Early postoperative prognostic indicators for IOP control to lower normal level and prolonged hypotony in trabeculectomy with mitomycin C were examined to determine conditions required to obtain an optimum balance between them. METHODS: Records of initial trabeculectomy with mitomycin C (0.4 mg/ml, 3 min) in 59 consecutively operated Japanese patients with primary open-angle glaucoma who had used multiple medications before operation were retrospectively analyzed. IOP control to lower normal level was defined as having failed if IOP could not be maintained below 15 mm Hg without medication. Prolonged hypotony was defined as postoperative IOP below 5 mm Hg for more than 2 months, excluding the first month. The Cox proportional hazards model was applied to identify early postoperative factors contributing to the two surgical outcomes. RESULTS: Among the factors studied, only the mean IOP on postoperative days 9-14 was significantly correlated with the surgical outcome. A receiver operating characteristic plot suggested that mean IOP of 8 mm Hg in this period would give an optimum balance between the two. CONCLUSION: IOP of 8 mm Hg 9-14 days after surgery may be advisable in patients with preoperative multiple medications in whom IOP control to lower normal level is attempted with mitomycin C trabeculectomy. Knowledge of this may be helpful in deciding when laser lysis of sutures is indicated.

Female↗

Posterior sub-Tenon's steroid injections for the treatment of posterior ocular inflammation: indications, efficacy and side effects.

PURPOSE: Posterior sub-Tenon's steroid injections (PSTSI) are a standard drug delivery method used for the treatment of chronic uveitis of the posterior segment. The aim of this study was to analyse the indications, efficacy and complications of PSTSI in the treatment of chronic uveitis. METHODS: During the period 1990-1994, 53 (9.5%) of 558 patients (58 eyes) followed up in the uveitis clinic received a total of 162 PSTSI of triamcinolone acetonide 40 mg in the superior quadrants. Indications for treatment were vision inferior or equal to 0.7 and/or intolerable visual disturbance. Only patients in whom PSTSI were the only treatment parameter changed were analysed. Among the main parameters analysed were visual acuity, aqueous laser flare photometry, intraocular pressure (IOP) and complications. RESULTS: Anatomical location of uveitis was as follows: anterior HLA-B27-related uveitis with CME (1 patient/1 eye), intermediate uveitis (28/32), posterior uveitis (10/10) and panuveitis (14/15). Mean duration of follow-up was 448+/-57 days. Visual acuity improved significantly from 0.40+/-0.03 to 0.79+/-0.07, with 59.4% of eyes having a gain of 2-5 Snellen lines and 18.7% a gain of >5 lines. Mean aqueous flare photometry decreased significantly from 29.6+/-3.5 to 13.6+/-2.2 photons/ms. Mean IOP increased significantly from 13.6+/-0.5 to 18.5+/-0.8 mm Hg with a rise of pressure >8 mm Hg in 23 cases (36%), transient in 16 cases, but chronic in 6 cases, needing filtering surgery. Partial superior ptosis was seen in two cases and cataract progressed in seven cases. CONCLUSION: PSTSI are very effective in restoring visual acuity in chronic uveitis of the posterior segment, without systemic complications, but at the expense of intraocular hypertension, a complication that was found more frequently than expected.

Adolescent↗

Late glaucoma after interstitial keratitis.

In a systematic study of 45 patients who had syphilitic interstitial keratitis early in life and, many years later, were discovered to have glaucoma, there was evidence of two different but equally common mechanisms. In one group of patients, a deep-chamber type of glaucoma was superimposed on old inflammatory changes, was characteristically refractory to medical treatment, but did well with filtering surgery. The other group of patients had reversible angle-closure glaucoma associated with anatomically small anterior segments, and typically responded well to iridectomy. The late, refractory, deep-chamber type of glaucoma may involve endothelialization and formation of glass membrane in the angle, as seen in one excised eye. Occurrence of the shallow-chamber, reversible angle-closure type of glaucoma after interstitial keratitis may be coincidental, since no other evidence supports the idea that small anterior segments might be particularly prevalent among patients who have had congenital syphilis or interstitial keratitis.

Adult↗

Clear-cornea cataract extraction in eyes with functioning filtering blebs.

In 22 glaucomatous eyes with functioning filtering blebs and adequately controlled intraocular pressures (less than or equal to 22 mm Hg) that underwent clear-cornea cataract extraction, the intraocular pressure remained controlled in 20 (91%). Seven of the 21 eyes, however, required an increased dosage of antiglaucoma drugs. Sixteen eyes had final visual acuities between 6/6 and 6/9 (20/20 and 20/30) and only four eyes had final visual acuities worse than 6/60 (20/200). The only intraoperative complication was a ruptured lens capsule. Postoperative bullous keratopathy developed in two eyes, both of which had had corneal edema postoperatively. A third eye, which had undergone filtering surgery 17 years earlier, had vitreous incarceration after the sutures were removed.

Aged↗

Argon laser trabeculoplasty in younger patients with primary open-angle glaucoma.

We conducted a retrospective comparison of the effectiveness of argon laser trabeculoplasty in controlling increased intraocular pressure in two different age groups treated for medically uncontrolled primary open-angle glaucoma. Of 15 eyes of patients less than 40 years old who had primary open-angle glaucoma, nine (60%) had uncontrolled intraocular pressures postoperatively and needed filtering surgery within two years of argon laser trabeculoplasty. Only two of 29 (7%) eyes in older patients had unacceptably high intraocular pressures during a mean (+/- 1 S.D.) follow-up period of 17 +/- 5 months. Older eyes had greater decreases in intraocular pressure (12 +/- 6 mm Hg) than younger eyes (5 +/- 6 mm Hg) after laser treatment. Failure in young eyes appeared to correlate with a high preoperative intraocular pressure. Thus, argon laser trabeculoplasty is not a reliably effective form of therapy for younger patients with primary open-angle glaucoma.

Adolescent↗