|Year : 1990 | Volume
| Issue : 1 | Page : 17-19
Role of 5 fluorouracil in the management of failed glaucoma surgery
NN Sood, Harsh Kumar, HC Agarwal, Ramanjit Sihota
R.P. Centre for Ophthalmic Sciences, New Delhi-29, India
N N Sood
R.P. Centre for Ophthalmic Sciences, New Delhi-29
Source of Support: None, Conflict of Interest: None
Filtering surgery for glaucoma usually controls the intraocular pressure adequately. However, in glaucoma patients with aphakia, neovascularisation of iris, previous failed filtering surgeries and relatively young patients, results of surgery leave much scope for improvement. Most failures of filtering surgery are related to extra-ocular factors. Histopathological studies of eyes after failed filtering operations have suggested that proliferation of fibroblasts and deposition of collagen constitute a barrier to filteration. There is also a positive correlation between success of filtering surgery and inhibition of fibroblast growth by the patients aqueous humour. Thus agents inhibiting fibroblast proliferation should play an important role in increasing the success rate of filtering surgery. 5 Fluorouracil is a pyrimidine analogue which has been utilised for over 15 years as an antimetabolite in cancer therapy. Its efficiency in inhibiting fibroblast proliferation in vitro and in rabbit eyes has been proved beyond doubt. We undertook a pilot project to estimate the efficiency of the subconjunctival 5 FU to increase the changes of success in problematic cases of glaucoma in pigmented eyes.
|How to cite this article:|
Sood N N, Kumar H, Agarwal H C, Sihota R. Role of 5 fluorouracil in the management of failed glaucoma surgery. Indian J Ophthalmol 1990;38:17-9
|How to cite this URL:|
Sood N N, Kumar H, Agarwal H C, Sihota R. Role of 5 fluorouracil in the management of failed glaucoma surgery. Indian J Ophthalmol [serial online] 1990 [cited 2020 Dec 5];38:17-9. Available from: https://www.ijo.in/text.asp?1990/38/1/17/24554
| MATERIAL & METHODS|| |
Only cases having previously undergone an unsuccessful glaucoma filtering surgery were included in this study. All eyes underwent a detailed routine ophthalmic examination including applanation tension, gonioscopy and visual fields.
All eyes underwent a trabeculectomy in a quadrant 180° away from the previous filtering site where possible and 90 o away in others. A fornix based conjunctival flap was used in all cases. A triangular scleral flap was raised and a block of trabecular tissue 3 x 1 mm was excised. A peripheral iridectomy was performed and the scleral flap was closed by three 10-0 monofilament sutures. Subconjunctival 5 fluorouracil was given from the first postoperative day at 180' away from the site of the bleb in a dose of 0.1 ml containing 5 mgs.,Close post-operative watch was kept on corneal staining, wound leak and anterior chamber depth. Subsequent injections were given on alternate days depending upon the above factors. Massage was carried out routinely in all eyes
with deep chambers and high IOPs. Post surgery all patients were kept on 20 mg oral and local steroid for a period of one week after which the drugs were tapered.
| Observations|| |
All the six eyes in the study belonged to male patients, ages ranging from 18 to 60 years. All had at least one unsuccessful surgery for open angle glaucoma. Unsuccessful surgery was defined as a post-operative condition in which the intra ocular tension measured by Applanation remained morethan 22 mmHg inspite of maximum topical antiglaucoma medication. Eyes 1 & 2 belonged to an 18 year old patient with juvenile glaucoma who had been unsuccessfully operated 3 times in both eyes previously. Eyes 3 and 4 belonged to a 40 year male with open angle glaucoma who had once undergone filtering surgery without any success. Eye No.5 belonged to a 60 year old male patient who had healed uveitis and failed trabeculectomy. Eye No.6 belonged to a 50 year male patient with open angle glaucoma once operated by trabeculectomy but did not remain under control. The total dose of 5 FU given subconjuctivally in each patient along with the complications faced during the study are enumerated in [Table - 1][Table - 2] respectively. The average follow-up of the patients were 5 months and all the eyes except eye No.6 were controlled. Only the No.2 eye still requires topical medication for adequate control of IOP. The definition of success was taken as a normal diurnal variation (maximum applanation tension less than 22) with or without topical antiglaucoma medication.
| Discussion|| |
A few studies are now available on the relative safety and efficiency of the 5 FU as adjunctive therapy postoperatively in patients with glaucoma with poor prognosis for success of surgery ,,9. 5 FU is a halogenated pyrimidine analogue. In vivo Fluorouracil is converted to 5 monophosphate nucleotide (F-UMP) which interacts with enzyme hyonidylate synthetase and is regarded as the principle site of cytotoxic action of the drug. Fluorouracil is much more lethal to logarithmically growing cells than to stationary cells. The blockade of honidylate synthetase reaction inhibits the DNA synthesis while cellular production of both RNA and proteins continues. An imbalance in growth occurs which is not compatible with cell survival.
Its systemmic dosage is 10-15 mg/kg body weight I.V. once a day. As only 5 mg per 0.1 ml is to be used on alternate days subconjunctivally, a vial will have to be broken and discarded. If stored in a cool place, precipitates may form which are to be dissolved and the drug warmed to room temperature before use. Antimetabolities besides 5 FU which have been tried with variable results include Trifluorothymidine, doxorubicin, daunarubicin, bleomycin and cytarabine. Other chemnicals like Beta amino propionitrile (BAPN) and D penicillamine which inhibit collagen cross linkage are also being tried 10.
A study done at the Bascom Palmer Eye Institute utilising 5 FU revealed success rates of 75% at 3 years follow up of phakic eyes with previously failed filtering surgery . Another study at University of California, San Deigo reported a succes of 92% in patients with 2 previously failed surgeries in phakic non-neovascular glaucomaa. The above success of 5FU in failed filtering surgeries was demonstrated in Western eyes.
In Indian eyes our experience suggests an excellent response in maintaining patency of filtering blebs. It was successful in controlling intraocular presure in all the patients with preveiously failed filtering surgery except in case no. 6 where the development of uveitis forced us to abandon the therapy.
The dose of subconjunctival 5 FU should not be kept fixed but should vary according to corneal complications and chamber depth.
5 FU is available in the Indian market as Fivefluro from Biddle Sawyer in 50 mg per ml injection or as Fluracil of Biochem in 5 ml ampoule containing 250 mg.
The main complication faced was the corneal epithelial defects. Fifty percent of the eyes had a positive staining though it was severe enough only in one eye to warrant the postponement of subsequent doses of 5 FU. Corneal filament was seen in one of the eyes but disappeared promptly on removal and bandaging for 24 hours after which the drug was restarted without subsequent recurrence. Eye no. 2 also developed a subepithelial scarring in the form of a 4 mm line running just above the pupillary area. This scarring was still present 3 months after the last follow up though it did not impede vision. Corneal complications have been reported by other authors as well. ,11,12 Shallow AC as result of wound leak was seen in 2 of the 6 eyes. This complication is to be expected because the drug itself retards wound healing. However, none of the shallow chambers persisted for a long time. Only one of our cases showed an unusual picture of uveitis which healed with steroids. Overall experience suggests an excellent efficacy of 5 FU in maintaining the patency of filtering blebs with few complications. The injections are painful and the stay in the hospital is prolonged for close monitoring.
| Summary|| |
A pilot study was undertaken in 6 pigmented eyes of Indian patients to prove the safetly and efficacy of subconjunctival 5 Fluorouracil in maintaining the patency of filtering blebs. All eyes had previously undergone an unsuccessful filtering surgery. An average of 27.5 mg of 5 FU was injected 180- away from the bleb site in 5 mg alternate day doses. Intraocular pressure was controlled in five out of the six eyes after an average follow up of 5 months. Of the five controlled eyes only one eye required additional medication after filtering surgery and 5 FU therapy. Main complicatiions included corneal epithelial defects (50%), corneal filaments (16 6%) subepithelial fibrosis (16.6%), shallow chamber (33.2%) and uveitis (16.6%).
| References|| |
Maumence AE. External filtering operations for glaucoma the mechanism of function and failure. Trans. Am. Ophthalmol. Soc. 58:319-25.1969
Cohen JS, Shaffer RN, Hethrington J Jr., Hoskins D Revision of filteration surgery. Arch. Opthalmol. 95: 1612-5. 1977
Van Buskik EM. Cysts of Tenons capsule following filtering surgery. Am. J. Ophthalmol. 94: 522-7 1982
Teng CC, Chi HH, Katzin HM. Histology and mechanism of filtering operations. Am. J. Ophthalmol. 47:16-31. 1959
Herschler J; Claftin, AJ, Florentino G. The effect of Aqucous humour on the growth of subconjunctival fibroblasts in tissue culture and its implications for gI licoma surgery. Am. J. Ophthalmol. 98:245-9. 1980
Blumaenkranz M: Ophir A, Claflin A. Pharmacological approach to non neoplastic intra ocular proliferation. ARVO abstracts Invest. Ophthalmol. vis. Sci 20(Suppl.) 200. 1981
Rockwood, EJ, Parrish RK, Heuer DK et al. Glaucoma filtering surgery with 5-Fluororacil. Ophtahlmology; 87;94. 1987
Weinreb RN. Adjusting the dose of 5-Fluorouracil after filteration surgery to minimize side effects. Ophthalmology, 94,564-70.1989
[Table - 1], [Table - 2]