Corticosteroid-induced glaucoma attributable to an adrenocorticotropin-secreting malignant carcinoid tumor of the thymus.

PURPOSE: To describe the clinical and histopathologic findings in a patient with corticosteroid-induced open-angle glaucoma attributable to an adrenocorticotropin-secreting malignant carcinoid of the thymus. METHODS: Case report. In a 33-year-old man, the clinical course, laboratory findings, and imaging results as well as the histopathologic findings are described. RESULTS: Increased intraocular pressure in this patient represented a manifestation of severe hypercortisolism attributable to a malignant adrenocorticotropin-secreting carcinoid tumor. Surgical removal resulted in return of the intraocular pressure values to normal levels. CONCLUSION: Thymic carcinoid is a rare cause of Cushing syndrome, which can lead to increased intraocular pressure.

Late-onset, bleb-associated endophthalmitis following glaucoma filtering surgery with or without antifibrotic agents.

The use of adjunctive antimetabolites such as 5-fluorouracil (5-FU) and mitomycin C (MMC) in trabeculectomy has caused an increased concern as to the risk of bleb-associated endophthalmitis. In this study, we compared the incidence of this complication between different methods of adjunctive treatment in glaucoma filtering surgery. Records of 15 cases of late-onset, bleb-associated endophthalmitis which were admitted to the Ophthalmology Department, Hadassah University Hospital, between January 1980 and December 1997 were retrospectively studied. These patients had endophthalmitis at least two months following glaucoma filtering surgery. Bleb-associated endophthalmitis occurred in 2 eyes following filtering surgery with no antifibrotic agent, in 6 eyes following trabeculectomy with 5-FU, and in 7 eyes that underwent trabeculectomy with intraoperative MMC. The mean time from surgery to endophthalmitis following 5-FU was 25.0+/-22.0 months (range 3 to 56 months), and 11.3+/-5.4 months (range 4 to 18 months) following the use of MMC. The estimated cumulative incidences of bleb-associated endophthalmitis in superior blebs at 24 months following surgery were 0.3% for surgeries without antifibrotic agents, 0.8% for trabeculectomies with postoperative 5-FU, and 1.3% for trabeculectomies with intraoperative MMC. No significant differences were demonstrated between the survival distributions of filtering procedures performed with any of the three techniques (p = 0.166, Log-rank test). Most of the cases following 5-FU or MMC appeared within 18 months following trabeculectomy. The visual outcome of most of the eyes was poor. Antifibrotic agents are not associated with a higher risk for late-onset, bleb-associated endophthalmitis. A high rate of alertness is warranted for diagnosis of early signs of infection following glaucoma filtering surgery.

Mitomycin-C in combined or two-stage procedure trabeculectomy followed by penetrating keratoplasty.

PURPOSE: To evaluate the efficacy and safety of application of mitomycin-C (MMC) in combined and separate trabeculectomy and penetrating keratoplasty for the treatment of coexisting corneal disease and glaucoma. METHODS: A retrospective evaluation of 11 eyes of 10 patients was conducted. A combined trabeculectomy with MMC and penetrating keratoplasty procedure was performed in eight eyes (group 1), and keratoplasty was performed after a previous trabeculectomy with MMC in three eyes (group 2). RESULTS: In group 1, seven of the eight eyes had controlled intraocular pressure (IOP) and clear corneal graft at the end of the follow-up period (range, 5-60 months; mean duration, 16.7 months). In group 2, all three eyes had controlled IOP at the end of the follow-up period (range, 4-30 months; mean duration, 14 months); two of these patients had clear corneal grafts, and graft failure occurred in the remaining patient. Complications included transient flat anterior chamber and corneal epithelial defects, each of which occurred in a single eye in group 1, and progressive cataract, which occurred in a single eye in group 2. CONCLUSION: Mitomycin-C was found to be safe and efficient in the present series, controlling IOP in 10 of 11 eyes (91%) with coexisting corneal disease and glaucoma. The transplanted corneas remained clear in 9 of 11 eyes (82%). Complications related to MMC included a reversible epithelial defect that occurred in one eye.

A comparative study of two dose regimens of latanoprost in patients with elevated intraocular pressure.

OBJECTIVE: The purpose of the study was to determine whether latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor PGF2a-isopropyl ester), a new prostaglandin analogue that has been found effective in reducing intraocular pressure (IOP) in humans, is equally effective at lower concentrations than those currently employed. DESIGN AND PARTICIPANTS: Fifty patients with glaucoma or ocular hypertension were treated in a randomized, crossover, double-masked fashion with 1 drop of latanoprost (50 microg/ml once daily and 15 microg/ml twice daily) in the affected eye(s) for 3 weeks on each concentration. Tonometry was obtained at 8:00, 13:00, and 17:00 hours at baseline (untreated) and after 3 weeks on each concentration. Placebo (a buffer solution of latanoprost eye drop) was administered for complete masking of the study. RESULTS: Mean baseline (untreated) diurnal IOP for the entire sample was 24.7 mmHg. Intraocular pressure was reduced by 6.1 mmHg with latanoprost 15 microg/ml twice daily, and by 7.5 mmHg with 50 microg/ml once daily. Results with both regimens were significant (P < 0.001 each, Student's t-test). However, the 50 microg/ml dose was significantly more effective than the 15 microg/ml dose, with a difference of 1.4 mmHg (P < 0.001, ANOVA). Both dose regimens were well tolerated, with little, predominantly mild, ocular discomfort. The higher dose did not cause more hyperemia at 3 weeks than the lower one, i.e., the lower dose yielded a slightly higher score (1.8 mm) on the visual analogue scale (P < 0.29, ANOVA). CONCLUSIONS: Latanoprost administered at a concentration of 50 microg/ml once daily effectively reduces IOP in patients with elevated IOP. Administration of a lower concentration (15 microg/ml) twice daily is less effective, but still significant.

Filtering surgery with 5-fluorouracil subsequent to Molteno implant.

In cases of refractory glaucoma, when Molteno shunt implantation has been performed and resulted in failure, the best surgical option has not yet been established. Filtering surgery with 5-fluorouracil (5-FU) as one option for the above was performed in four non-neovascular glaucomatous eyes (four patients) after failure of Molteno shunt implantation. Injections of 5 mg 5-FU were administered once daily for 9-14 days. After follow-up of 6-18 months in 3 eyes, intraocular pressure ranged from 10 to 16 mm Hg. In the fourth eye, in which bleb scarring ensued, a second filtering surgery with 5-FU was performed after 4 months, and resulted in a successful outcome as recorded 26 months later. These preliminary results suggest that filtering surgery with 5-FU might be an acceptable surgical option in non-neovascular refractory glaucoma subsequent to failure of Molteno shunt implantation.

Late complications after glaucoma filtering surgery with adjunctive 5-fluorouracil.

We studied 105 patients (105 eyes) operated on for glaucoma with adjunctive fluorouracil, who were followed up for 12 to 48 months (mean, 34.6 +/- 12.9 months). Fifty eyes that had previous glaucoma or cataract extraction or had inflammatory glaucoma had a high risk for postoperative scarring (high-risk group), and 55 eyes had glaucoma surgery as an initial procedure (initial surgery group). An intraocular pressure of 20 mm Hg or less, with or without hypotensive medications, was found in 42 eyes in the high-risk group (84.0%) and in 53 of the eyes in the initial surgery group (96.4%). Of the 105 eyes, an intraocular pressure of 12 mm Hg or less without medication was achieved in 17 eyes in the high-risk group (34.0%) and in 35 eyes in the initial surgery group (63.6%). Late complications in both groups were as follows: endophthalmitis in four eyes (3.8%) (two of the infected blebs were located superiorly and two inferiorly), transient leaking bleb in two eyes (1.9%), hypotony of an extended period with 180 to 360 degrees of filtration in three eyes (2.9%), giant bleb extending over the cornea in two eyes (1.9%), and a transient, mild iridocyclitis in nine eyes (8.6%). Thus, adjunctive fluorouracil after filtering surgery may entail various, mainly bleb-related, late side effects and complications.

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.

A randomized study of trabeculectomy and subconjunctival administration of fluorouracil in primary glaucomas.

Forty-one adult patients with primary open angle glaucoma and nine adult patients with chronic angle closure glaucoma underwent trabeculectomy in one eye each. Twenty-one eyes with primary open angle glaucoma and four with chronic angle closure glaucoma were randomly assigned to receive four to six subconjunctival injections of fluorouracil for 10 days after surgery. Twenty-five control eyes did not receive fluorouracil. Intraocular pressure was 20 mm Hg or lower in 24 eyes (96%) in the treatment group after mean follow-up of 17.8 months and in 19 control eyes (76%) after mean follow-up of 17.5 months (P less than .05). Encapsulated bleb developed in three (12%) of the fluorouracil-treated eyes vs two (8%) of the control eyes. A few injections of fluorouracil adequately inhibited scarring. This might be explained by its toxic effect on existing fibroblasts. Overall, trabeculectomy with injection of fluorouracil was found to be efficacious and relatively safe. Further studies regarding late complications are required.

Encapsulated filtering bleb and subconjunctival 5-fluorouracil.

Filtering bleb encapsulation (BE) involves fibroblast proliferation and collagen synthesis. We analyzed the effect of 5-fluorouracil (5-FU) on the inhibition of BE. Forty-one patients with primary open-angle glaucoma underwent trabeculectomy in one eye as an initial surgery. Twenty-one of these eyes, randomly chosen, were treated postoperatively with four to six 5-FU subconjunctival injections over 10 days to inhibit bleb scarring; the remaining 20 eyes did not receive 5-FU. After 12 to 24 months, the surgical success rate was significantly higher in the treated eyes (P less than .05). However, the incidence of BE was similar: two eyes (9.5% and 10%, respectively) in each group. The difference between the effect of 5-FU in the inhibition of BE and bleb scarring suggests that the characteristics of the two fibroblast populations are heterogeneous.

Delayed filtering bleb encapsulation.

Encapsulated filtering blebs concomitant with increased intraocular pressure (IOP) developed 47 and 6 months, respectively, after surgery in two women, 46 and 60 years old, respectively, who had undergone trabeculectomy operations in one eye. Both blebs were associated with mild anterior uveitis. Following treatment with topical steroids, cyclopentolate, hypotensive medications, and digital massage, the uveitis resolved and the IOP fell. The likely cause of these late-appearing encapsulated blebs was anterior uveitis.

Toxic effects of 5-fluorouracil on fibroblasts following trabeculectomy.

The inhibitory effect of 5-fluorouracil (5-FU) on fibroblast proliferation is well established. In addition, toxic effects of 5-FU on existing fibroblasts, in rabbits and in vitro, were demonstrated. We examined human subconjunctival scar tissue which was removed during Molteno tube implantation. Surgery was performed 9 weeks after filtering surgery with 5-FU that resulted in bleb scarring. In the tissue, intracytoplasmic vacuoles were detected in some myofibroblasts, with no visible collagen in their vicinity. This presumed toxic effect of 5-FU may be one explanation for the adequacy of fewer than twice 5-FU injections daily following filtering surgery, and for less than 14 days, as originally recommended for inhibiting bleb scarring.

[Treatment of anterior uveitis with 5-fluorouracil].

Filtering surgery with use of 5-fluorouracil (5FU) was performed in 5 eyes (4 patients) with inflammatory glaucoma to prevent filtering bleb scarring. Postoperative injections of 5FU were given once or twice a day, according to the degree of anterior chamber inflammation. Complete remission of the uveitis was achieved in all 5 eyes after 7-14 days of postoperative injections of 5FU. There were no recurrences of uveitis during a minimum of 8 months of follow-up.

Regulating the dose of 5-fluorouracil to prevent filtering bleb scarring.

Repeated doses of 5mg of 5-fluorouracil (5-FU) were injected subconjunctivally in 25 poor-prognosis glaucomatous eyes after filtering surgery to prevent filtering bleb scarring. The frequency (1-2 times a day) and duration (minimum, 7 days) of injections were determined by the degree of the anterior chamber reaction and/or conjunctival hyperemia at the filtering bleb site. Punctate corneal erosions or filaments were not considered a contraindication to continuation of 5-FU treatment. After 12 months, intraocular pressure (IOP) of 16 mmHg or less without medical treatment was found in 19 (76%) eyes. In 16 of these (64%), the IOP was 12 mmHg or less. In two (8%) other eyes, it was 20 mmHg or less with medication. We believe that the comparatively low IOP levels achieved without medical treatment in 76% of the eyes in our study can be attributed in part to our therapeutic approach with 5-FU.

Subconjunctival 5-fluorouracil and herpes simplex keratitis.

We present a case of herpes simplex keratitis that appeared during a period following filtering surgery in which subconjunctival 5-FU was being administered. Although the 5-FU treatment was not halted, 4 days later the keratitis healed. The typical practice of discontinuing 5-FU treatment when these kinds of inflammation occur following filtering surgery may be unwarranted.

[Prevention of scarring of filtering bleb by 5-fluorouracil].

Scarring of the filtering bleb is the most common cause of failure of surgery for glaucoma. It is much more common when the surgery is for certain types of glaucoma, such as aphakic glaucoma, cases of previously failed filtering surgery and neovascular and uveitic glaucoma. In 31 such high-risk cases we injected 5-fluorouracil subconjunctivally for 7-16 days after operation to prevent scarring of the filtering bleb. The success rate was 83%. After a follow-up of 3-12 months, there was statistically significant improvement in each group as compared to cases in which the drug was not administered. Further indications should be considered for the use of 5-fluorouracil in glaucoma.

A functional vagotomy induced by unilateral forced right nostril breathing decreases intraocular pressure in open and closed angle glaucoma.

There is evidence of the central regulation of intraocular pressure, and it has been suggested that vagal tone might be increased in glaucoma simplex. The nasal cycle, the simultaneous congestion-decongestion response in the nasal cavities, reflects the dynamic lateralisation of the autonomic nervous system. Since this lateralisation presents with sympathetic activity induced by left brain hemisphere stimulation and parasympathetic activity induced by right hemisphere stimulation, it was subsequently demonstrated that forced unilateral nostril breathing induces selective contralateral hemispheric stimulation as measured by relative increases in the electroencephalographic amplitude in the contralateral hemisphere as well as alternating lateralisation of plasma catecholamines. Using this functional vagotomy, we report that left hemispheric stimulation by 20 minutes of forced unilateral right nostril breathing led to a significant bilateral decrease of 4.6 mmHg (25%) in intraocular pressure in 46 patients with open and closed angle glaucoma. However, it significantly increased the IOP in three patients with neovascular, one with juvenile onset, and one with closed angle glaucoma.

Filtering surgery with 5-fluorouracil: a second course.

In five glaucoma patients, a previous filtering surgery that was followed by sub-conjunctival injections of 5-Fluorouracil (5-FU) failed, due to filtering bleb scarring. A repetition of the filtering surgery with subsequent sub-conjunctival injections of 5 mg of 5-FU, administered once daily for 8-14 days, was undertaken. At the end of 6-19 months of follow-up, IOP levels in all five eyes were 20 mmHg or less with medication. A repeated course of filtering surgery plus 5-FU treatment seems to be a favourable surgical option in refractory glaucoma.