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Adjunctive subconjunctival mitomycin C in glaucoma triple procedure.

PURPOSE: To evaluate the potential benefit of adjunctive subconjunctival mitomycin in patients with primary open-angle glaucoma undergoing primary trabeculectomy combined with phacoemulsification and intraocular lens implantation. METHODS: Seventy-eight eyes of 78 patients with primary open-angle glaucoma with visually symptomatic cataracts and no previous incisional surgery were randomized to receive either no mitomycin C or a subconjunctival application of 1-, 3-, or 5-minute mitomycin C (0.5 mg/ml). RESULTS: Follow-up (mean +/- standard deviation) was 21.0 +/- 7.7 months. The mean postoperative intraocular pressures were significantly lower with significantly less medications than the preoperative values at each follow-up time (1, 3, 6, 9, 12, 15 months, and last follow-up) for all groups (P < 0.05 for each). However, there was no significant difference at each follow-up time in intraocular pressure, medications, or best-corrected visual acuity among the four groups or between the control and the total mitomycin C group. CONCLUSION: Adjunctive subconjunctival mitomycin C did not further improve the final intraocular pressure outcome of the primary trabeculectomy combined with phacoemulsification and intraocular lens implantation in patients with primary open-angle glaucoma. Future studies will determine the appropriate role, if any, for adjunctive mitomycin C in selected primary glaucoma triple procedures.

Aged↗

Adjunctive mitomycin C in Molteno implant surgery.

PURPOSE: The authors assessed the efficacy of adjunctive intraoperative mitomycin C to produce lower intraocular pressures (IOPs) in patients with complicated glaucoma who underwent double-plate Molteno implantation. METHODS: A pilot series of 21 consecutive patients who underwent double-plate Molteno implantation with adjunctive intraoperative mitomycin C (0.5 mg/ml) for 5 minutes was compared with a historical control group who received Molteno implants without mitomycin C (n = 18). With failure defined as an IOP greater than 21 or less than 6 mmHg at two observations 1 month apart, the addition of medication, re-operation for glaucoma, or tube removal, a life-table analysis of IOP was performed on patients with at least 3 months' follow-up. RESULTS: Success in the mitomycin C group was higher (68% at 1 year) than the control group (17% at 1 year; P = 0.006). Loss of more than one line of vision (33%) and re-operation for complications (including flat anterior chamber, choroidal detachment, and tube blockage) (38%) were slightly but not significantly more frequent in the mitomycin C group than in the control group. CONCLUSION: This study suggests that intraoperative mitomycin C in conjunction with Molteno implant may offer a better chance of achieving target IOPs in the low teens in patients with complicated glaucoma than Molteno implantation alone.

Adult↗

The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery.

BACKGROUND: The use of adjunctive intraoperative mitomycin C has considerably improved the success rate of glaucoma filtering surgery. However, the ideal concentration and exposure time of mitomycin C is unknown. The purpose of this study is to determine whether a satisfactory surgical outcome can be achieved with a lower incidence of adverse side effects by using a shorter exposure time of mitomycin C than has been recommended previously. METHODS: Twenty-five eyes of 25 consecutive patients who were considered to be at high risk for surgical failure because of their age (< 55 years), previous failure of trabeculectomy, previous cataract surgery, or traumatic glaucoma received a single intraoperative application of mitomycin C (0.2 mg/ml for 2 minutes). They were case-matched with a group of 48 consecutive patients who received a single intraoperative application of mitomycin C (0.2 mg/ml for 5 minutes) by using age, race, type of refractory glaucoma, and preoperative intraocular pressure (IOP) as variables. RESULTS: Eighteen months after surgery, 22 (88%) patients in the 2-minute group and 21 (84%) patients in the 5-minute group had an IOP less than 21 mmHg with or without treatment. No significant differences were found in the complication rate: in 2 (8%) of 25 eyes of the 2-minute group, chronic hypotony developed compared with 3 (12%) of 25 eyes in the 5-minute group. Hypotony-related maculopathy developed in one eye in the 5-minute group. A cystic bleb was found in 15 (60%) eyes in the 2-minute group compared with 19 (76%) eyes in the 5-minute group, although this difference was not statistically significant. Two (8%) eyes in the 2-minute group and one eye (4%) in the 5-minute group had a bleb-related infection. In one (4%) patient in each group, late severe endophthalmitis developed. CONCLUSION: These results suggest that a 2-minute intraoperative application of 0.2 mg/ml mitomycin C is as effective as a 5-minute exposure, but the complication rate remains unaltered.

Adult↗

One-year follow-up results of combined mitomycin C trabeculectomy and extracapsular cataract extraction.

PURPOSE: When patients with glaucoma require cataract surgery, combined procedures offer important advantages over cataract surgery alone. Because mitomycin C has improved the success rate of a trabeculectomy in patients at high risk for filtration failure, the authors investigated whether it also would increase the survival rate of functioning filters in combined procedures. METHODS: Patients with both cataract and glaucoma underwent combined mitomycin C trabeculectomy, extracapsular cataract extraction, and intraocular lens implantation. Mitomycin C (0.5 mg/ml) was applied topically to the trabeculectomy site for 5 minutes before the cataract extraction. Intraocular pressure (IOP), visual acuity, and astigmatism were measured preoperatively and postoperatively. One-year results are available for 74 patients. RESULTS: At 1 year, 54 (73%) of 74 patients had IOPs of 15 mmHg or less without glaucoma medications. Visual acuity was 20/40 or better in 44 (60%) of 74 patients. Ten (15%) patients had a shift of more than 2 diopters of astigmatism against the rule compared with preoperative values. No notable corneal epithelial toxicity was present. Postoperative symptomatic hypotony with the wound construction occurred in 3 (4%) of 74 patients, with 1 patient requiring surgical revision. Other potential complications of mitomycin C include endothelial toxicity (1 patient had decreased vision due to endothelial folds) and wound stability (1 patient had wound rupture after direct ocular trauma). CONCLUSION: The 1-year survival rate of a functioning trabeculectomy using mitomycin C in combined glaucoma and cataract surgery is encouraging. The longer-term benefits and possible adverse effects of mitomycin C in combined procedures are unknown and continue to be investigated.

Adult↗

5-Fluorouracil and mitomycin C in pseudophakic patients.

PURPOSE: Previous studies have shown that 5-fluorouracil (5-FU) and mitomycin C enhance the success rate of filtration surgery in aphakic eyes. However, eyes with posterior chamber implants have not been specifically studied. This study was performed to compare the safety and efficacy of 5-FU with that of mitomycin C in eyes that have posterior chamber implants and undergo filtration surgery for uncontrolled glaucoma. METHODS: Eighty eyes of 74 patients who had previous cataract surgery with posterior chamber implants and who subsequently required trabeculectomy for uncontrolled open-angle glaucoma were randomized to receive either subconjunctival postoperative 5-FU or intraoperative mitomycin C. RESULTS: Twelve months after surgery, intraocular pressures (IOPs) averaged 12.8 +/- 5.5 mmHg (mean +/- standard deviation) in the mitomycin C group and 14.8 +/- 3.8 mmHg in the 5-FU group (P = 0.001). Mitomycin C-treated eyes received an average of 0.6 medications for IOP control, and 5-FU-treated eyes received an average of 1.05 medications (P = 0.03). There was no significant difference in complications between the two groups. CONCLUSION: Mitomycin C appears to be a viable alternative to 5-FU in patients with posterior chamber implants with uncontrolled glaucoma who require filtration surgery.

Aged↗

A comparative study of recurrent pterygium surgery: limbal conjunctival autograft transplantation versus mitomycin C with conjunctival flap.

OBJECTIVE: To compare the recurrence rate following treatment of recurrent pterygia using one of two techniques-limbal conjunctival autograft transplantation versus low-dose intraoperative mitomycin C (0.2 mg/ml) combined with conjunctival flap closure. DESIGN: Randomized clinical trial. PARTICIPANTS: Eighty-one patients with recurrent pterygia treated by limbal conjunctival autograft transplantation (n= 41) or mitomycin C combined with conjunctival flap (n= 40) participated. INTERVENTION: Limbal conjunctival autograft transplantation or low-dose intraoperative mitomycin C application with conjunctival flap technique was performed on recurrent pterygium cases. MAIN OUTCOME MEASURES: Recurrence of pterygium and postoperative complications. RESULTS: During mean follow-up periods of 16+/-1.9 and 15.5+/-1.5 months, six recurrences (14.6%) in the limbal conjunctival autograft transplantation group and five recurrences (12.5%) in the mitomycin C group were observed (P=0.77). The difference between the mean ages of recurrent (26.4+/-8.0 years) and nonrecurrent (35.8+/-11.9 years) cases for all patients was statistically significant (P=0.014). Technically, limbal conjunctival autograft transplantation seemed to be more difficult. The most frequent complication in limbal conjunctival autograft transplantation was graft edema, whereas that in the mitomycin C group was superficial keratitis. CONCLUSION: Both techniques showed similar recurrence rates in the treatment of recurrent pterygia. Although technically easier to perform, further follow-up is necessary to determine the long-term safety of low-dose intraoperative mitomycin C with conjunctival flap closure. The surgeon's familiarity with either procedure should determine the method of choice.

Adult↗

Phenethyl isothiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo.

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p < or = 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by mitomycin C.

Animals↗

Effects of mitomycin C on the oxygenation and radiosensitivity of murine and human tumours in mice.

BACKGROUND AND PURPOSE: Mitomycin C was one of the first chemotherapeutic agents to be shown to have preferential cytotoxicity toward hypoxic cells in vitro. Consequently, it has been used clinically with radiotherapy, and has stimulated considerable interest for analogue development. More recent studies also suggested a possible role for the drug in enhancing tumour blood flow; we therefore undertook a comprehensive examination of mitomycin C as a potential radiosensitizer in murine and human tumours growing in mice. MATERIALS AND METHODS: Two dissimilar human tumour xenograft systems, SiHa and WiDr cells, were used as was the murine SCCVII line. Effects of mitomycin C treatment on the regional and microregional blood flow in these tumours was evaluated, and cell sorting based on dye perfusion techniques was used to study the cytotoxicity of mitomycin C as a single agent or in combination with radiation in the xenograft systems. RESULTS: Contrary to our expectations, no preferential killing of less-well oxygenated tumour cells in situ was observed, nor were any consistent effects on tumour blood flow found. The inclusion of mitomycin C with radiation did, however, produce a modest increase in cell killing in the hypoxic subpopulations of the xenograft system with the largest hypoxic fraction. CONCLUSIONS: Our results indicate that combined treatment with mitomycin C and radiation cannot be rationalized on the expectation of either complementary cytotoxicity of the modalities, or of drug-induced improvement in tumour oxygenation.

Animals↗

Use of mitomycin C for maintaining myringotomy patency.

The purpose of this study was to determine whether topical mitomycin C could be used to prolong the patency of a myringotomy site in the absence of a ventilation tube. Mitomycin C is an antineoplastic agent used to maintain a patent trabeculectomy site in patients with glaucoma. The KTP laser was used to create bilateral myringotomies 0. 4 mm in diameter in 28 chicks (Gallus domesticus). Mitomycin C was applied to the right myringotomy site, and sterile water, used as a control, was applied to the left myringotomy site. The animals were divided into 2 groups with group A treated with freshly prepared mitomycin C and group B treated with 2-week-old mitomycin C. The patency rates of the experimental ears of groups A and B were 80% and 70%, respectively, 15 days after surgery and 33% and 7.7%, respectively, at 30 days. All myringotomy sites in the control ears were healed within 5 days. Using a logistic regression model for repeated measures, we determined the odds ratio between the experimental and control myringotomies of the combined groups to be 149.1 (P = 0.0001). We conclude that mitomycin C had a significant effect in prolonging the patency of myringotomies in chick tympanic membranes.

Administration, Topical↗

Endoscopic treatment of laryngeal and tracheal stenosis-has mitomycin C improved the outcome?

OBJECTIVE: The management of laryngeal and tracheal stenosis remains a challenging problem despite advances in endoscopic surgical techniques. Scar formation and restenosis is the main cause of failure, and this study assesses the efficacy of two adjuvant treatments: endoscopic steroid injection and topical mitomycin C application. Study design and setting This is a retrospective cohort study comparing the efficacy of 3 endoscopic techniques: (1) carbon dioxide (CO(2)) laser incisions with bronchoscopic dilatation, (2) CO(2) laser with dilatation followed by steroid injection into the stenotic area, and (3) CO(2) laser with dilatation followed by topical application of mitomycin C. Included in the statistical analysis were 47 procedures performed by the senior investigator in a tertiary medical center between 1994 and 2001 based on their success or failure. RESULTS: The percentages of successful outcomes in the study groups were 15%, 18.2%, and 75% with the CO(2) laser, CO(2) laser with steroid injection, and CO(2) laser with mitomycin C, respectively. Statistical comparisons reveal that the differences in outcomes were statistically significant (P < 0.05) between the mitomycin group and each of the other two treatment groups, whereas there was no statistically significant difference between the laser only and laser with steroid groups. There were no complications noted with the use of adjuvant medications. CONCLUSION: These patient group results indicate a statistically significant increase, from <20% to 75%, in the success rate of endoscopic treatment of acquired upper airway stenosis when topical mitomycin C is added to the treatment regimen. No benefit has been demonstrated for using intraoperative local steroid injections as an adjunct to laser treatment. Clinical significance Mitomycin C appears to be an effective and safe adjuvant treatment in the endoscopic management of laryngeal and tracheal stenosis.

Administration, Topical↗

Preventing myringotomy closure with topical mitomycin C in rats.

The purpose of this study was to determine whether mitomycin C could be used to prolong the patency of the myringotomy site in the absence of ventilation tubes in rats. We examined the effect of increased exposure time and repeat application of mitomycin C to the myringotomy site. Sixty animals were separated into 4 groups: group A had a single application of mitomycin C for 10 minutes; group B had a single application for 20 minutes; group C received 2 10-minute applications separated by 1 week; and group D received 2 applications (20 and 10 minutes) separated by 1 week. Mitomycin C and bacteriostatic saline solution were applied to the right and left myringotomy sites in each rat, respectively. Experimental ears in groups A, B, C, and D remained open for a median time of 6.5, 5.5, 6.5, and 8.5 weeks, respectively. The control ears healed within 1. 5 weeks. This difference was statistically significant with P < 0.001 for each group. We conclude that mitomycin C is effective in prolonging the patency of myringotomies in rat tympanic membranes. Increased exposure time or repeat application of mitomycin C did not statistically alter the patency rate.

Administration, Topical↗

Effect of mitomycin-C on posterior capsule opacification in rabbit eyes.

PURPOSE: To determine whether mitomycin-C can inhibit posterior capsule opacification (PCO) without causing ocular toxicity. SETTING: Yonsei Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. METHODS: Mitomycin-C dissolved in sodium hyaluronate (0.2 cc of 0.2 mg/mL) was injected into the empty capsular bag for 3 minutes after endocapsular phacoemulsification in rabbit eyes. Three months after surgery, the obstruction rate of visible light caused by PCO was measured using an optical power meter. RESULTS: The mean obstruction rate of visible light was 81.0% +/- 8.3% (SD) in the control group in which sodium hyaluronate without mitomycin-C was used, 30.5% +/- 10.1% in the group in which mitomycin-C was dissolved in sodium hyaluronate, and 71.9% +/- 6.8% in the group in which mitomycin-C was dissolved in a balanced salt solution. Statistically significant differences were found among all 3 groups. CONCLUSIONS: Our results suggest that the application of mitomycin-C dissolved in sodium hyaluronate effectively reduces PCO in rabbit eyes.

Adjuvants, Immunologic↗

Development of new mitomycin C and porfiromycin analogues.

New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data.

Animals↗

Lack of influence of the carbamoyl group on the stereochemistry of the acid-catalyzed opening of the aziridine ring of the mitomycins and of congeners.

The acid-catalyzed opening of the aziridine ring of mitomycins A and C is known to occur predominantly with cis stereochemistry. We have observed that the presence or absence of a carbamoyl group at C-10 of mitomycin C and in certain of its analogues does not have a significant influence on the stereochemistry of the opening of this ring. The trans product obtained from mitomycin C was shown to be stable when treated with acid under the conditions of its formation. Mitomycin B was also shown to yield predominantly the cis product when it was subjected to acid-catalyzed opening of its aziridine ring. The 1H NMR spectra of acetate derivatives prepared from mitomycin B show two sets of signals that are due to two populations of rotamers. The analysis of these spectra has substantiated several previous spectral assignments. This paper also presents some thoughts on acid-catalyzed bifunctional DNA alkylation by mitomycins and 10-decarbamoyloxy-9-dehydromitomycins.

Chemical Phenomena↗

Type III and type IV hypersensitivity reactions due to mitomycin C.

A 71-year-old man developed an exfoliative dermatitis of the palms of the hands and soles of the feet, and a generalized itch, during treatment with intravesical instillations of mitomycin C for an undifferentiated carcinoma of the bladder. Patch tests with mitomycin C 0.03%, 0.1% and 0.3% aq. were positive. Because of the serious consequences of this finding, the patient was retested with mitomycin C in pet. (same concentrations), a more stable preparation. This showed clear positive reactions. During this last series of patch tests, he developed palpable purpura on the legs. We postulated that this reaction was an immune-complex-mediated reaction, caused by the 2nd series of patch tests with mitomycin C. To prove this, we performed histopathological and immunofluorescence investigations, and these showed the reaction to be consistent with Henoch-Schonlein-type purpura. We therefore conclude that this patient developed systemic reactions to mitomycin C, characterized by an eczematous dermatitis as well as purpuric reactions. The intravesical installations with mitomycin C have been stopped. The patient's skin problems (the purpura as well as the eczema) have completely resolved and have not recurred.

Administration, Intravesical↗

7-N,7'-N'-(1",2"-Dithianyl-3",6"-dimethylenyl)bismitomycin C: synthesis and nucleophilic activation of a dimeric mitomycin.

Dimeric alkylating agents that modify complementary DNA strands have engendered significant interest. We have prepared the novel dimeric mitomycin, 7-N,7'-N'-(1",2"-dithianyl-3",6"-dimethylenyl)bismitomycin C (9), in which the mitomycins are bridged by a dithiane unit. Dimer 9, like the clinically tested acyclic disulfides KW-2149 (3) and BMS-181174 (4), was designed to activate under nucleophilic and reductive conditions. Successive nucleophile-mediated disulfide cleavage transformations of 9 are expected to generate thiol species ideally positioned to render the two mitomycin systems vulnerable to nucleophilic attack and permit DNA interstrand cross-link formation. The dithiane linker, strategically positioned between the two mitomycins, distinguished 9 from 3 and 4. Nucleophilic activation of this cyclic disulfide permitted both activated mitomycins to remain tethered to one another. We report the synthesis of 9, and show that the nucleophile Et(3)P markedly enhances the activation and consumption of 9, compared with the reference compound 7-N, 7"-N'-(cyclohexanyl-trans-1",4"-dimethylenyl)bismitomycin C (27). We further demonstrated that provides higher levels of DNA interstrand cross-links than either the dimeric reference compounds, and 7-N,7-N'-(2",5"-dihydroxy-1",6"-hexanediyl)bismitomycin C (28), or the monomeric mitomycins, 1 and 3, when Et(3)P is added to solutions containing EcoRI-linearized pBR322 DNA.

Binding Sites↗

[Topical Mitomycin C for the prophylaxis of recurrent haze after excimer laser photorefractive keratectomy (PRK) - a pilotstudy of 5 patients].

PURPOSE: Corneal haze is a severe complication after excimer laser PRK and may lead to a compromised visual performance and regression. Currently, corticosteroids are topically applied to inhibit the appearance of haze. However, this therapy is not always successful in preventing haze. Various animal studies have shown that topical applied mitomycin C reduces keratocyte activity and collagen synthesis and subsequently haze. MATERIAL AND METHODS: We have treated 5 patients (5 eyes) with severe haze and regression after PRK. In all eyes we have mechanically debrided the haze and 0.02 % mitomycin C was applied to the area of previous ablation for 1 minute. In 2 eyes we have only performed the debridement, whereas in 3 eyes we also have performed a re-PRK after the laser ablation the mitomycin was applied. The postop follow-up was 9 months. RESULTS: In all eyes the surgery and the postop time was without any complications. The haze could be removed in all eyes completely and in the entire postop period recurrent haze was not more than trace. Regression could be eliminated in the three eyes with a re-PRK, whereas the 2 eyes without re-PRK still remained myop. We could not observe any mitomycin C associated complications on the conjunctiva or cornea. CONCLUSION: Topical applied mitomycin C seems to be a promising therapy to prevent recurrent haze after a second PRK procedure. As mitomycin C can be associated with a variety of serious complications, it should only be used in patients with high risk of haze.

Adult↗

[Effect of local administration of mitomycin C on intraocular pressure].

BACKGROUND: Animal studies suggest that the decrease of intraocular pressure after application of mitomycin C is particularly mediated by toxic effects on the substance of ciliary body. Moreover it has been shown that the concentration of mitomycin C after topical application in the aqueous humour is as high when performing fistulating surgery. In this prospective study we wanted to investigate whether the topical application of mitomycin C would result in a significant decrease of intraocular pressure. PATIENTS AND METHODS: Forty-one eyes of 41 patients underwent pterygium surgery using a bare sclera technique. Afterwards phototherapeutic keratectomy with the excimer laser (193 nm) was performed in the area of the excision. In hospital mitomycin C eye drops (0.02%) were given twice daily for four days. The intraocular pressure of treated and untreated eyes was measured with applanation tonometry at least three times per day preoperatively, postoperatively at the fourteenth day and after 6 month. RESULTS: Mean intraocular pressure of the treated eyes was preoperatively 15.73 +/- 2.35 mm Hg, 14 days postoperatively 15.92 +/- 2.79 mm Hg and at the last examination 15.86 +/- 2.39 mm Hg. For untreated eyes the mean intraocular pressure was preoperatively 15.70 +/- 2.04 mm Hg, after 14 days 15.76 +/- 2.96 mm Hg and at the last examination 15.89 +/- 2.67 mm Hg. Consequently there was no statistically significant change of intraocular pressure in the eyes treated with mitomycin C. Furthermore there were no significant differences of intraocular pressure between treated and untreated eyes at any time of postoperative check-up. CONCLUSION: The short-term local application of mitomycin C did not result in a detectable change of intraocular pressure and is therefore probably an alternative to intraoperative application during filtration surgery.

Adult↗