Augmented trabeculectomy in paediatric glaucoma.

AIMS: To report the experience with trabeculectomy augmented with mitomycin C and 5-fluorouracil for the treatment of paediatric glaucoma. METHODS: Retrospective, interventional case series design was used. The sample included 17 children (29 eyes) with primary (19 eyes) or secondary (10 eyes) glaucoma who were treated with augmented trabeculectomy as the primary procedure between 1990 and 2002. Data were collected on age and family history, preoperative and end of follow up intraocular pressure, cup/disc ratio (evaluated by drawing), visual acuity, complications, and post-surgery treatment. RESULTS: Patient age at surgery ranged from 1 month to 8 years; most patients (n = 14, 82.3%) were aged less than 1 year (range 1 month-8 months, mean 3.95 (SD 2.56) months); three patients (17.7%) were aged 3, 5, and 8 years. The duration of follow up was 3-120 months (mean 46 months). Intraocular pressure significantly improved from 21 mm Hg to 60 mm Hg (mean 33.1 (10) mm Hg) before surgery to 6-26 mm Hg (mean 17.1 (6) mm Hg) after, (p <0.0001). There was no significant change in cup/disc ratio: 0.1-0.8 (mean 0.42 (0.26)) before and 0.1-1.0 (mean 0.511 (0.27)) after (p = 0.45). In 22 eyes (75.8%), intraocular pressure was controlled at less than 20 mm Hg and the cup/disc ratio remained stable or improved. The life table success rate for intraocular pressure control remained stable at 86% at the 12, 24, and 36 months and after 48 months decreased to 53%. There was no significant difference in the life table results between primary and secondary glaucoma. 14 eyes (48.2%) had a visual acuity better than 20/120 by the end of follow up. Repeated surgery was necessary in eight eyes (27.5%), and additional antiglaucoma treatment in 13 (44.8%). Complications included retinal detachment 1 year after surgery, choroidal detachment, and blebitis (one eye each). CONCLUSIONS: Augmented trabeculectomy with mitomycin C and 5-fluorouracil may serve as the primary procedure in a selected group of paediatric patients with glaucoma.

Matrix metalloproteinase-1 localization in the normal human uveoscleral outflow pathway.

PURPOSE: To determine the distribution of matrix metalloproteinase-1 (MMP-1) in the uveoscleral outflow pathway and other anterior segment tissues of normal human eyes. METHODS: Normal human eyes were fixed in methacarn and sectioned and immunostained using a specific polyclonal antibody to MMP-1. Immunoreactivity was visualized using diaminobenzidine. To compare the staining intensity in various tissues, the mean optical density within the ciliary body, mid-iris stroma, iris root, uveal trabecular meshwork, cornea, and sclera was determined using imaging densitometry. To determine the cellular distribution of MMP-1 in ciliary muscle, additional sections were double-immunostained using antibodies to MMP-1 and calponin. These sections were examined by confocal laser scanning microscopy. Specificity of the antibody to MMP-1 in ocular tissues was confirmed by western blot analysis with uveal tract homogenates. RESULTS: Moderate-to-strong MMP-1 immunoreactivity was observed in ciliary muscle, iris, sclera, corneal endothelium, and ciliary nonpigmented epithelium. Lighter immunoreactivity was observed in corneal epithelium, blood vessels, trabecular meshwork, Schlemm's canal, and associated collector channels. Confocal microscopy showed that ciliary muscle MMP-1 was primarily inside ciliary muscle cells. Densitometry showed that net optical density was approximately fivefold greater in ciliary muscle, iris root, and sclera than in trabecular meshwork. CONCLUSIONS: MMP-1 was prominently identified in regions of the anterior segment of normal human eyes associated with the uveoscleral outflow pathway and in the iris, corneal endothelium, and ciliary nonpigmented epithelium. These data support the hypothesis that MMP-1 activity is involved in regulating uveoscleral outflow facility.

Reduced TIGR/myocilin protein in the monkey ciliary muscle after topical prostaglandin F(2alpha) treatment.

PURPOSE: Mutations in the trabecular meshwork inducible glucocorticoid response (TIGR) gene, also known as myocilin, have recently been linked to some forms of glaucoma. Recent studies have shown that TIGR protein also is expressed in the ciliary muscle. Because uveoscleral outflow, which traverses the ciliary muscle, is increased by prostaglandins (PGs), the present study assessed whether topical PGs alter the amount of TIGR protein within the ciliary muscle. METHODS: Vehicle was topically applied to one eye, and 2 microg PGF(2alpha)-isopropyl ester (PGF(2alpha)-IE) was applied to the other eye of cynomolgus monkeys twice daily for 5 days. Pressure reductions of 5 mm Hg in the PGF(2alpha)-IE-treated eyes were confirmed. The eyes were then fixed and paraffin sections were cut from each eye. The distribution of TIGR protein in the ciliary muscle was determined by confocal scanning laser microscopy. Additional sections were immunostained with a polyclonal antibody to recombinant TIGR protein or with a polyclonal antibody to a synthetic peptide corresponding to the leucine zipper region within the TIGR protein. Staining intensity in the ciliary muscle was assessed by measuring optical density (OD) along two line segments overlying the ciliary muscle, by using a high-resolution imaging densitometer. RESULTS: TIGR protein immunoreactivity was observed in ciliary muscle fibers throughout the ciliary muscle. Extracellular TIGR immunoreactivity colocalized with collagen type IV immunoreactivity. Intracellular staining also was present. Immunoreactivity was less intense in the sections from the PGF(2alpha)-IE-treated eyes compared with the vehicle-treated eyes. This was reflected in the reduction of mean OD scores in each monkey. Overall, the reduction of mean OD scores in the treated eyes was 42.1% +/- 9.9% (P < 0.005) with the anti-recombinant TIGR antibody and 27.3% +/- 10.4% with the anti-TIGR peptide antibody (P < 0.005). CONCLUSIONS: TIGR protein immunoreactivity was present both intracellularly and extracellularly in the ciliary muscle of the cynomolgus monkey. This suggests that extracellular TIGR protein is in contact with aqueous humor in the uveoscleral outflow pathway. Moreover, IOP-lowering topical PGF(2alpha)-IE treatment decreases the amount of TIGR protein in the ciliary muscle.

Reduction of collagen type I in the ciliary muscle of inflamed monkey eyes.

PURPOSE: To investigate in monkey ciliary muscle the relationship between the extent of anterior segment inflammation and alterations of collagen type I as determined by quantitative imaging densitometry. METHODS: Anterior segment inflammation was induced in one eye of five cynomolgus monkey by cannulation of the anterior chamber, by anterior chamber injection of bovine serum albumin, or by disruption of the iris and anterior lens capsule with a needle. Increases in inflammatory cells were scored in hematoxylin and eosin-stained sections. Parallel eye sections were immunostained for collagen type I and developed using diaminobenzidine. Optical density (OD) was measured along two line segments overlying the immunostained ciliary muscle using two-dimensional imaging densitometry. To assess antibody labeling of ciliary muscle structures, additional sections were double-immunostained using antibodies to collagen type I and calponin and examined by confocal microscopy. RESULTS: In each of the inflamed eyes, hematoxylin and eosin-stained sections showed signs of chronic inflammation including lymphocytes and macrophages dispersed among ciliary muscle fibers and in the iris. Double label confocal microscopy showed collagen type I immunoreactivity in the interstitial extracellular matrix between bundles of ciliary smooth muscle fibers. Collagen type I OD scores in each of the inflamed eyes were less by 16% to 55%, compared with the contralateral control eyes. The mean of the OD scores for all inflamed eyes was 39%+/-7% less than the mean of the control eye scores (mean +/- SEM, P < 0.001). Regression analysis showed a close correlation between inflammatory cell scores in the treated eyes and the reduction of OD scores (r = 0.94, P = 0.02). CONCLUSIONS: These results indicate that the density of collagen type I in the extracellular matrix (ECM) of monkey ciliary muscle is reduced during anterior segment inflammation and support the view that reduction of ciliary muscle ECM may contribute to increased uveoscleral outflow facility during anterior segment inflammation.

Increased matrix metalloproteinases 1, 2, and 3 in the monkey uveoscleral outflow pathway after topical prostaglandin F(2 alpha)-isopropyl ester treatment.

OBJECTIVE: To investigate the effects of topical prostaglandin F(2 alpha)--isopropyl ester (PGF(2 alpha)-IE) administration on immunoreactivity of matrix metalloproteinases (MMPs) 1, 2, and 3 within the anterior segment tissues of monkey eyes. METHODS: Eight eyes from 4 cynomolgus monkeys were evaluated. One eye from each monkey was treated with 2 mg of PGF(2 alpha)-IE twice daily for 5 days, and intraocular pressure reduction was measured. After fixation and processing, deparaffinized sections of anterior segments were immunostained using antibodies to MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), or MMP-3 (stromelysin-1). Optical density along 2 line segments overlying the iris root, ciliary muscle, and adjacent sclera and perpendicular to their long axes was measured using imaging densitometry. RESULTS: Compared with the contralateral vehicle-treated eyes, statistically significant increases in optical density scores were observed in the iris root, ciliary muscle, and adjacent sclera for all 3 MMPs (P<.01). In these tissues, MMP-1 immunoreactivity was increased by a mean +/- SD of 89% +/- 16%, 61% +/- 8%, and 66% +/- 57%, respectively; MMP-2 immunoreactivity by 129% +/- 53%, 82% +/- 27%, and 267% +/- 210%, respectively; and MMP-3 immunoreactivity by 207% +/- 84%, 83% +/- 49%, and 726% +/- 500%, respectively. CONCLUSIONS: Treatment of monkey eyes with PGF(2 alpha)-IE induces elevation of MMP-1, MMP-2, and MMP-3 in tissues of the uveoscleral outflow pathway. These increases suggest that MMPs might play an important role in the increased uveoscleral outflow observed with topical prostaglandin treatment. CLINICAL RELEVANCE: Immunoreactivity of MMPs in tissues of the monkey uveoscleral outflow pathway is increased after topical treatment with PGF(2 alpha)-IE. This response also might be involved in the intraocular pressure--lowering effect of other prostanoids used to treat glaucoma.

Topical prostaglandin F2alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway.

BACKGROUND: Topical prostaglandin F2alpha isopropyl ester increases uveoscleral outflow in monkeys and humans. OBJECTIVE: To investigate the effects of prostaglandin F2alpha isopropyl ester with topical administration on collagen types I, III, and IV within the anterior segment tissue of monkey eyes. METHODS: Eight eyes of 4 cynomolgus monkeys were evaluated. One eye of each monkey was treated with 2 microg of prostaglandin F2alpha isopropyl ester twice daily for 5 days, and intraocular pressure reduction was confirmed. These eyes were fixed in methacarn, and paraffin sections were immunostained using antibodies to collagen types I, II, or IV. To measure staining intensity, optical density (OD) was determined using 2-dimensional imaging densitometry. Mean OD scores along line segments placed over the ciliary muscle were determined. RESULTS: Mean+/-SD OD scores for collagen types I, III, and IV were less in the ciliary muscle of prostaglandin-treated eyes than in vehicle-treated eyes by 52%+/-7%, 45%+/-6%, and 45%+/-5%, respectively. In the sclera adjacent to the ciliary body, mean OD scores for collagen types I and III were less in prostaglandin-treated eyes, by 43%+/-32% and 45%+/-13%, respectively. The scleral stroma was minimally immunoreactive for collagen type IV. All differences were significant by the paired Student t test (P<.05). CONCLUSIONS: This study shows reduced collagen types I, III, and IV immunoreactivity in the ciliary muscle and adjacent sclera following topical prostaglandin F2alpha isopropyl ester treatment. These reductions may contribute to the increased uveoscleral outflow observed with topical prostaglandin treatment. CLINICAL RELEVANCE: The cellular mechanism by which certain prostaglandins lower intraocular pressure is not known. The present study provides immunohistochemical data demonstrating that intraocular pressure reduction that occurs with topical prostaglandin F2alpha is associated with a reduction of collagens within the uveoscleral outflow pathway.

Three-dimensional measurements of central serous chorioretinopathy using a scanning laser tomograph.

PURPOSE: To evaluate the topographic three-dimensional mapping of retinal elevation in central serous chorioretinopathy using the Heidelberg Retina Tomograph and to correlate the measured parameters with the fluorescein angiographic findings. METHODS: Seventy-six consecutive patients with central serous chorioretinopathy (63 men, 13 women), between 26 and 54 years of age, were examined to identify areas of neurosensory retinal detachment and fluorescein leakage. In areas of retinal detachment, the parameters measured were the area, volume, maximal height, and diameters of the retinal elevation, which were statistically analyzed, and the correlations between these parameters were evaluated. RESULTS: Mean +/- SD area of elevation was 9.6 +/- 5.22 mm2 (range, 2.7 to 21.5 mm2); mean volume was 1.16 +/- 1.3 mm3 (range, 0.11 to 4.73 mm3); mean maximal height was 238 +/- 108 microns (range, 97 to 450 microns); mean x-axis was 3.4 +/- 1.1 mm (range, 1.6 to 5.6 mm); and mean y-axis was 3.03 +/- 0.98 mm (range, 1.6 to 4.7 mm). Most of the retinal elevations were oval (the x-axis longer than the y-axis); the maximal height was in the geometric center in the smaller blebs and below the geometric center in the larger blebs. There were statistically significant correlations between area, volume, and height of the sensory elevation. No correlation was found between the location and the shape of leakage on fluorescein angiography and the Heidelberg Retina Tomograph measurements. CONCLUSIONS: Confocal laser tomography is potentially useful as a noninvasive diagnostic technique for quantitative measurements of the neurosensory retinal detachment in central serous chorioretinopathy.

Indocyanine green angiographic findings in nonproliferative diabetic retinopathy.

PURPOSE: To report angiographic findings of nonproliferative diabetic retinopathy patients by means of indocyanine green angiography. METHODS: Forty-two eyes (42 patients) with nonproliferative diabetic retinopathy were evaluated by indocyanine green angiography in addition to fluorescein angiography. Angiographic findings with the two imaging techniques were compared with the red-free fundus appearance. RESULTS: Among the 42 eyes, five (12%) had the appearance on indocyanine green angiography of lobular spotty hyperfluorescent and hypofluorescent areas ("salt and pepper" appearance) in the very late phase. Twenty eyes (48%) presented with diffuse late-phase hyperfluorescence on indocyanine green angiography, corresponding to areas of retinal capillary nonperfusion on fluorescein angiography, and retinal edema. A total of 3,564 microaneurysms were divided into three types: 58 (1.6%) appeared mainly on the fluorescein angiography and very faintly on the indocyanine green angiography, 3,029 (85%) appeared on the fluorescein angiography and the indocyanine green angiography, and 477 (13.4%) were uniquely hyperfluorescent on the indocyanine green angiography. CONCLUSIONS: Indocyanine green angiography in patients with nonproliferative diabetic retinopathy disclosed microvascular findings that were in addition to those shown on fluorescein angiography. These angiographic changes were not observed on fluorescein angiography because of imaging limitations. Indocyanine green angiography may be a useful adjunct to fluorescein angiography in the evaluation of chorioretinal vascular changes in nonproliferative diabetic retinopathy.

Pupillary block following posterior chamber intraocular lens implantation in adults.

BACKGROUND: Pupillary block rarely occurs after cataract extraction with posterior chamber intraocular lens implantation. METHODS: A series of six patients (seven eyes) treated for pupillary block after posterior chamber intraocular lens implantation between 1990 and 2001 is described; in one eye, the attack occurred after phacoemulsification. RESULTS: The interval between pupillary block development and the cataract surgery ranged from 1 day to 5 years. In all eyes, treatment consisted of neodymium-YAG laser peripheral iridotomy. In four eyes, the laser peripheral iridotomy relieved the block (one procedure in two; two to three procedures in two). One patient was also treated with YAG capsulotomy, and two patients needed additional surgical intervention. CONCLUSION: Despite the rarity of the complication of pupillary block after posterior chamber intraocular lens implantation, physicians should be aware of the sometimes difficult course of recovery after treatment.

Evaluation of bilirubin as possible protective factor in the prevention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) appears to be a multifactorial disease, the prevention of which is probably impossible even with the most accurate methods of blood-gas monitoring and oxygen restrictions. The oxidative processes and consequent formation of free radicals are probably influenced by the availability of various antioxidants in the immature retina. Bilirubin, the end product of haem catabolism, has recently been regarded as a potential physiological antioxidant. In order to test the suggestion as to the possible effect of bilirubin in reducing the incidence of ROP a retrospective study was undertaken of the medical records of 151 neonates born between 1984 to 1988 who weighed less than 1500 g. Of these, 78 had various degrees of ROP, whereas 73 had no ROP and served as a control group. The daily mean bilirubin values were analysed in accordance with gestational age and birth weight as well as the severity of ROP, and the results were compared with those obtained for the control group. The results showed no correlation between bilirubin levels and severity of ROP in all subgroups of gestational age and birth weight. These findings indicate that there is no apparent protective effect of bilirubin on the development of ROP.

Eleven years' experience with retinopathy of prematurity: visual results and contribution of cryoablation.

We report our 11 years' experience of cryotherapy for retinopathy of prematurity (ROP). Charts of 624 infants weighing under 1250 g who were admitted to our Neonatal Intensive Care Unit during 1977-87 were reviewed. Three hundred and eighty nine babies survived, and the total ROP prevalence was 57.5%. Cryotherapy was applied to 35%. Only one case (0.25%) of blindness was detected, and four babies (1%) had a final visual acuity of less than 20/200 in one eye. The complication rate following cryoablation was very low.

Non-retinovascular leakage in diabetic maculopathy.

BACKGROUND: Diabetic macular oedema is the leading cause of vision deterioration in diabetic retinopathy. Extracellular fluid within the retina, which distorts the retinal architecture, was assumed to be strictly of retinal vasculature origin. However, there is some experimental evidence supporting clinical observations suggesting a possible role of the retinal pigment epithelium (RPE). An unusual form of diabetic maculopathy is presented in which the RPE and the subretinal space play the main role. METHODS: Fluorescein angiograms of 1850 non-proliferative diabetic retinopathy (NPDR) patients were examined. Nineteen eyes (14 patients, 1% of NPDR patients) met the criteria-mainly having minimal diabetic retinopathy with only a few microaneurysms and no clinically significant macular oedema (CSMO). Early phase angiograms were compared with late phase angiograms. RESULTS: It was found that in all 19 eyes the area of diffuse RPE late phase leakage was spread around the macular area. No cystic changes or cystoid macular oedema were present in any of the eyes and the visual acuity was 6/10 or better in all the eyes. CONCLUSIONS: Possible changes occur in the RPE that may be responsible for the late leakage in NPDR patients-namely, diabetic retinal pigment epitheliopathy. These changes are associated with a breakdown of the outer blood-retinal barrier, consisting of leakage through RPE cells. No focal or diffuse leakage across the RPE has been reported in the literature related to the fluorescein angiograms in diffuse diabetic maculopathy.

The effect of topical ceftazidime on pseudomonas keratitis in rabbits.

Ceftazidime is a beta-lactam antibiotic highly effective against Pseudomonas aeruginosa infection. Using a rabbit model of Pseudomonas keratitis, 10(3) bacteria (in 20 microliters) were injected unilaterally into the corneal stroma of albino rabbits. Twenty-six hours after inoculation, topical Ceftazidime (50 mg/ml) drops were administered for 48 h, following which the corneal tissue was cultured. Eighteen of 20 corneal cultures (90%) from rabbits treated with Ceftazidime drops were negative. In comparison, all untreated control group cultures showed florid bacterial growth. These results suggest that topical Ceftazidime may be a useful agent in the treatment of P. aeruginosa keratitis.

The pituitary-thyroid axis effects on ocular and orbital tissues: a histological, histochemical, and morphometric study.

This work tests the notion that the effect of thyroid hormone on orbital and ocular tissues is mediated through its action on their lysosomal enzymes. Hyperthyroidism was produced in guinea pigs by thyroxin and TSH; hypothyroidism was induced by thiouracil. After treatment for 10 to 21 days, several ocular and orbital tissues were taken for histological, morphometrical, and histochemical examinations. High acid phosphatase activity was demonstrated in extraocular muscles, optic nerve and the retinal pigment epithelium of thyroxine- and TSH-treated animals. The findings fit the notion that the effects of thyroid hormones are mediated through lysosomes also in ocular and orbital tissues.

Mitomycin C and 5-fluorouracil antimetabolite therapy for pediatric glaucoma filtration surgery.

PURPOSE: To evaluate the efficacy and safety of augmented trabeculectomy with 5-fluorouracil (5-FU) and mitomycin C (MMC) compared to 5-FU only for the treatment of pediatric glaucoma. PATIENTS AND METHODS: In a prospective randomized clinical trial, 8 children (12 eyes) with pediatric glaucoma, either congenital or secondary to: lens aspiration, Sturge-Weber syndrome, or steroids underwent augmented trabeculectomy. Six patients (8 eyes) underwent augmented trabeculectomy with 5-FU plus MMC and 2 patients (4 eyes) underwent augmented trabeculectomy with 5-FU only. MAIN OUTCOME MEASURES: Between-group comparison of postoperative parameters: change in intraocular pressure (IOP), dependence on antiglaucoma medication, number of 5-FU injections, cup-disc ratio, corneal diameter, drug-induced complications. RESULTS: In the 5-FU/MMC group, 7/8 eyes showed good control of postoperative IOP (9-16 mm Hg), which was independent of antiglaucoma therapy; only 2 injections of 5-FU were needed. By contrast, in the 5-FU group, no control of the postoperative IOP (21-23 mm Hg) was achieved in 4/4 eyes, and these patients remained dependent on antiglaucoma medication; up to 6 injections of 5-FU were used. There was no deterioration in the cup-disc ratio or the corneal diameter in either group. Results were maintained on follow-up (23-27 months). No significant drug-induced complications were noted. CONCLUSION: Augmented trabeculectomy with adjunctive 5-FU/MMC may be an option for the control of pediatric glaucoma in patients with a poor surgical prognosis.

[Prevalence of pigmentary dispersion syndrome in Israel].

Pigmentary dispersion syndrome is a precursor of pigmentary glaucoma whose prevalence in the urban population of USA was found to be 2.45%. We evaluated its prevalence during ocular screening examinations among normal Israelis. We screened for excessive pigmentation on the corneal endothelium with the slit-lamp and determined in each patient best corrected visual acuity, intra-ocular pressure (after mydriasis), condition of the anterior segment, cup-disk ratio, posterior segment abnormalities and questioned about history of any ocular disease and family history of glaucoma. 374 patients (mean age 49 +/- 11) were examined on 10 consecutive days. In 5.9% excessive corneal endothelial pigmentation was found. Intra-ocular pressure (after mydriasis) averaged 15.52 +/- 1.93 mm Hg as compared to 14.73 +/- 2.04 among the rest of our study population, (p = 0.01). The prevalence of suspected pigmentary dispersion syndrome among young adults in Israelis is high.