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Laser labyrinthectomy.

Concepts and methods of laser labyrinthectomy have been proposed based on experimental studies in which the macula utriculi was irradiated with an argon laser beam through the oval window. In our previous reports, a single application of the beam (1.5 W, 0.5 s) eradicated the guinea pig macula within 5 weeks. The contour of the membranous labyrinth was normal and intact. The human macula utriculi was approached after stapedectomy and irradiated with an argon laser in a patient who developed persistent positional vertigo after closure of a perilymph fistula. Laser singular neurectomy was also done. Hearing remained unchanged, and the patient's vertigo disappeared. The human macula sacculi, however, cannot be irradiated, because of the presence of pigment in the saccular wall. In guinea pigs, the semicircular canals were irradiated from the outside. The lateral and posterior canals were approached through the middle ear, whereas the anterior canal was approached through the posterior fossa. Argon laser irradiation (1-1.5 W, 0.5 s) to the bony canal produced a charred area with or without perforation. The semicircular duct showed shrinkage and tearing of the trabecular meshwork immediately after irradiation. Several weeks later, the canal had been obliterated by ossification. Although laser labyrinthectomy can destroy the function of individual otolithic organs and eliminate dynamic impulses of the semicircular canals, hearing can be preserved.

Animals↗

Aqueous humour and plasma cortisol levels in glaucoma and cataract patients.

By means of radioimmunoassay, the content of endogenous cortisol in the aqueous humour and plasma of 35 patients suffering from various types of glaucomas and 35 cataract patients was determined, and the ratio of the plasma to the aqueous humour cortisol levels was calculated. The highest cortisol level in both plasma and aqueous humour was found to occur in patients with open-angle glaucoma suffering at the same time from systemic hypertension. The lowest plasma to aqueous humour cortisol ratio was found in patients with secondary glaucoma treated with steroids. In woman suffering from open-angle glaucoma, the rising cortisol level in plasma with age contrasted to the decreasing cortisol level in aqueous humour. The authors suggest that there is an active interference with homeostatic mechanisms responsible for ensuring the stability of the eye inner milieu and a certain protection of the trabecular meshwork of the angle of the anterior eye chamber against noxious effects of the endogenous cortisol.

Adult↗

Pharmacological testing in the laser-induced monkey glaucoma model.

Glaucoma was induced in cynomolgus monkeys by photocoagulating the trabecular meshwork with the argon laser. Repeat treatments were often necessary and wide intraocular pressure fluctuations were characteristic. Baseline intraocular pressure was measured with a calibrated pneumatonometer hourly for six hours. On a succeeding day a baseline measurement was made, 50 microliter of the drug to be tested applied, and six hourly measurements of intraocular pressure repeated. The effects on intraocular pressure of timolol, epinephrine, pilocarpine, vanadate, prostaglandin F2 alpha (PGF2 alpha), forskolin, and corynanthine were tested in at least eight eyes. Significant (p less than 0.05) reductions of intraocular pressure were produced by 0.5% timolol, 2% epinephrine, 4% pilocarpine, 1% vanadate, 500 micrograms of PGF2 alpha and 1% forskolin. Five per cent corynanthine produced no significant lowering of intraocular pressure. Tonography revealed an increased outflow facility associated with the reduction of intraocular pressure 2 hours after the administration of 4% pilocarpine. This glaucoma animal model may be useful in investigating agents that lower intraocular pressure by a variety of mechanisms.

Administration, Topical↗

Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy.

Aqueous outflow resistance of enucleated human eyes was measured at 7 and 25 mm Hg before and after partial and complete (12 clock hours) internal trabeculotomy. Following complete trabeculotomy, 71% of the resistance was eliminated at 25 mm Hg while only 49% was eliminated at 7 mm Hg. In contrast to published findings in eyes with intact trabecular meshwork where the resistance increased with increasing IOP (1), following complete trabeculotomy, the resistance decreased 2% per mm Hg with increasing IOP. Experiments with trabeculotomy limited to part of the circumference showed that a one hour trabeculotomy produced 41% (25 mm Hg) to 60% (7 mm Hg) of the effect of a twelve hour trabeculotomy. The results indicate that a surprisingly high fraction of aqueous outflow resistance resides in the distal aspects of the outflow system at normal IOP, and that this distal resistance drops as IOP is increased.

Aged↗

The effect of MK-927, a topical carbonic anhydrase inhibitor, on IOP in glaucomatous monkeys.

MK-927 is a water soluble, potent inhibitor of human carbonic anhydrase (CA) II in vitro. Topical administration of MK-927 reduces intraocular pressure (IOP) in rabbits. Elevated IOP was produced in cynomolgus monkey eyes by argon laser photocoagulation of the trabecular meshwork. IOP was measured at 0 hr, 0.5 hr and hourly for 8 hrs in 8 eyes for two baseline days, one day on vehicle and five days of therapy with 2% MK-927 b.i.d., after initial single-dose trials of various concentrations. IOP was not significantly different comparing baseline and vehicle treated days. Significant (p less than 0.05) reductions of IOP occurred for five days lasting at least 8 hrs after each dosing. At 3 hrs after treatment with vehicle the IOP was 31.6 +/- 3.4 (SE) mm Hg. Maximum reduction of IOP occurred at 3 hrs after application of MK-927, the IOP decreasing from day 1 (19.9 +/- 1.0 mm Hg) to day 5 (16.5 +/- 1.6 mm Hg). MK-927 appears to have great clinical potential.

Administration, Topical↗

A comparison of L-671,152 and MK-927, two topically effective ocular hypotensive carbonic anhydrase inhibitors, in experimental animals.

L-671,152 is a water-soluble, carbonic anhydrase inhibitor structurally similar to MK-927, a carbonic anhydrase inhibitor that, on topical administration, lowers the intraocular pressure (IOP) of experimental animals and humans. L-671,152 was more potent than MK-927 at inhibiting purified, human erythrocyte carbonic anhydrase II in vitro, as reflected in their respective IC50 values of 0.16 nM and 1.19 nM. Both compounds were compared for topical, ocular hypotensive activity in pigmented rabbits and cynomolgus monkeys. Ocular hypertension was induced in the latter by argon laser photocoagulation of the trabecular meshwork. A 2% solution of L-671,152 was more potent than 2% MK-927 in lowering the IOP of ocular hypertensive monkeys, the maximum reductions being 13.8 mm Hg (37%) and 9.6 mm Hg (27%) at 5 hr and 4 hr, respectively. Moreover, the duration of action of L-671,152 was superior to that of MK-927. The ocular hypotensive effect of L-671,152 was greater than that of MK-927 over a range of concentrations (0.5%-2%) in pigmented rabbits whose IOP was inherently elevated. The peak declines in the IOP of these rabbits after the instillation of 2% solutions of L-671,152 and MK-927 were 6.1 mm Hg and 4.8 mm Hg, respectively. L-671,152 was very effective in lowering the elevated IOP of alpha-chymotrypsinized rabbits and the unilateral instillation of 0.5% L-671,152 into the contralateral eye failed to decrease the elevated IOP of the alpha-chymotrypsinized eye. This finding indicates that the site of action of topically applied L-671,152 is local. The enhancement in the potency of L-671,152 over MK-927 is attributed to a greater inhibition of carbonic anhydrase activity.

Administration, Topical↗

Egress route of emulsified 20 centistokes silicone oil from anterior chamber of rabbit.

Silicone oil is used in recent clinical practice, however, it may cause adverse reactions in the eyes. When the high viscosity silicone oil is contaminated with low molecular weight silicone oil, the contamination may cause ocular toxicity or elevation of the intraocular pressure. To obtain information on the distribution of this preparation, emulsified 20 centistokes silicone oil was injected into the anterior chamber of rabbit eyes. The silicone oil droplets were visualized by light and electron microscopy by using oil soluble phthalocyanine blue. This copper containing dye remains in the tissue after removal of the silicone oil by organic solvents. Two and 4 weeks after an injection, the silicone emulsion was observed as numerous small vacuoles with blue precipitate at the margin of vacuoles within elongated trabecular endothelial cells, fibroblasts along the route of uveoscleral outflow and cells of the iris. Three hours after the injection, only a few vacuoles were present in these cells. These results demonstrated that the emulsified silicone oil leaves the anterior chamber through the conventional and unconventional routes. Phagocytosis by the trabecular endothelial cells and fibroblasts along the uveoscleral route caused an accumulation of the emulsified silicone oil in these cells. With chronic exposure to emulsified silicone oil, changes in the trabecular meshwork may lead to a reduction in the outflow of aqueous humor and cause glaucoma.

Animals↗

Amyloid deposition in ocular tissues of patients with familial amyloidotic polyneuropathy (FAP).

It is known that the severity of ocular symptoms does not always correlate with the systemic symptoms in patients with familial amyloidotic polyneuropathy (FAP ATTR V30M). The ocular tissues may have their own TTR metabolic system. The aim of this study is to clarify the distribution of amyloid deposition in the ocular tissues and to investigate the relationship between ocular symptoms and histopathological changes. We analyzed histopathologically 9 autopsied eyes taken from 3 Japanese and 6 Swedish patients with FAP ATTR V30M. Localization of amyloid deposition varied among the different cases, but there were some tendencies in the distribution. The degree of amyloid deposition in the ocular tissues was not always correlated with the duration of the disease. The frequency of amyloid deposition in the conjunctiva, iris, trabecular meshwork and vitreous body were 88.9%, 44.4%, 11.1% and 11.1% respectively in the 9 patients. These frequencies in the histopathological changes correlated with the frequencies in the clinical ocular manifestations as previously reported.

Adult↗

Pseudoexfoliation syndrome--case report and review of clinical features.

Pseudoexfoliation syndrome is characterized by the presence of gray-white flakes on the pupillary borders and anterior lens capsule, increased trabecular meshwork pigmentation, and association with glaucoma. We describe 3 patients with this syndrome seen at Asan Meidcal Center Department of Ophthalmology in 1989, and we focus on their clinical features and management. We believe that patients with this syndrome are not as rare in Korea as has been thought, judging by scant report of cases in the past.

Aged↗

Familial isolated noncompaction of the ventricular myocardium in asymptomatic phase.

Isolated noncompaction of the ventricular myocardium (INVM) is a rare cardiomyopathy resulting from a failure of normal endomyocardial embryogenesis and it has been categorized as a form of unclassified cardiomyopathy. The disorder is characterized by an excessively prominent trabecular meshwork with deep intertrabecular recesses. Although the disorder is sporadic, familial incidence may occur. Clinical symptoms and prognosis of INVM may differ markedly, and range from an asymptomatic course to a severe cardiac disability. The diagnostic method of choice for IVNM is echocardiography, which reveals multiple prominent trabeculations with deep intertrabecular spaces communicating with the left ventricular cavity in the middle and apical segments of the left ventricle. The authors report a case of INVM in a family in which three adult members (a brother and two sisters) were found to be affected by this disorder. They were all asymptomatic. The diagnosis of the disorder was made first in the 36-year-old brother by transthoracic echocardiography (TTE) and multidetector CT (MD CT), during the process of preoperative evaluation for surgical treatment of low back intervertebral herniated disc. TTE and MD CT showed similar and peculiar findings of INVM. Echocardiographic screening in all first-degree relatives of this patient, in order to identify asymptomatic patients, demonstrated INVM in two elder sisters.

Adult↗

Congenital glaucoma and retinal dysplasia.

The differential diagnosis of leukocoria (pseudoglioma) in the neonate includes multiple conditions, including malformations with retinal dysplasia as a component. Typically bilateral, retinal dysplasia is characteristically seen in microphthalmic eyes. Certain chromosomal defects have been described. The case reported herein presented in the first month of life with an enlarged eye, elevated intraocular pressure, prominent iris vasculature, and leukocoria. Family history was positive in one respect: this is the second child of a Viet Nam veteran exposed to Agent Orange. The first child, from a different mother, also had birth defects. Other than his left eye, the child is completely normal. Ultrasonography showed posterior vitreous opacities of indeterminate configuration. CT scan suggested a posterior intraocular mass. Histologically, the principal features were an anomalous, largely unformed corneoscleral angle, intraocular hemorrhage, and retinal dysplasia. Light microscopic studies were performed. The corneoscleral angle revealed an anteriorly inserted iris with an absence of trabecular meshwork and Schlemm's canal. This case is considered unique on the basis of the association of retinal dysplasia with congenital glaucoma and larger-than-normal eye. The significance of reported paternal exposure to Agent Orange in this instance is unknown.

2,4,5-Trichlorophenoxyacetic Acid↗

One versus two simultaneous goniotomies as the initial surgical procedure for primary infantile glaucoma.

To evaluate whether a more extensive incision of the tissue adjacent to the anterior trabecular meshwork resulted in more effective control of intraocular pressure (IOP), seven infants with bilateral congenital glaucoma underwent a single goniotomy in one eye and two simultaneous goniotomies at separate sites in the second. Sodium hyaluronate (Healon) was used in all eyes undergoing two simultaneous goniotomies and in three to seven eyes undergoing a single goniotomy. Success was not significantly different, at 1 month or 1 year postoperatively, for eyes which underwent two simultaneous and separate goniotomies. Successful control of IOP was, however, related to the preoperative IOP. Eyes for which the initial procedure was unsuccessful had a significantly higher IOP. The incidence of postoperative hyphemas was less in eyes in which the Healon was used intraoperatively, but the use of Healon did not favorably or adversely affect intraocular pressure control.

Eye Diseases↗

Primary congenital glaucoma: 2004 update.

BACKGROUND: Primary congenital glaucoma is the most frequent childhood glaucoma and an important cause of blindness. We describe the current understanding regarding this disease, the evaluation of children with it, and its treatment. PATIENTS AND METHODS: We accessed information derived from a review of 287 patients with primary congenital glaucoma and current published data related to primary congenital glaucoma. RESULTS: The nomenclature for childhood glaucoma has been inconsistent, but is clarified for children with primary congenital glaucoma. The epidemiology of primary congenital glaucoma notes its variable incidence worldwide. Familial occurrence supports autosomal recessive transmission; chromosomal loci have been identified, and the CYP1B1 gene has been identified and clinically correlated. The histopathology of eyes with primary congenital glaucoma confirms the presence of a variable trabecular meshwork anomaly and the absence of an imperforate membrane. Children with primary congenital glaucoma are diagnosed after recognition of corneal signs and symptoms of glaucoma. CONCLUSIONS: The examinations of patients with primary congenital glaucoma must be thorough to distinguish this glaucoma from other types of childhood glaucoma, to prepare for surgery, and to follow progress with treatment. Medical treatment must be tailored to the pediatric patient. Goniosurgery is the definitive procedure of choice for most children with primary congenital glaucoma, but other procedures are also used successfully after goniosurgery fails or is determined to be inappropriate. Future success will be determined by physicians who sustain continued progress for children with glaucoma.

Child↗

Ocular changes in reactions in leprosy.

A study of ocular changes in reactions in leprosy was undertaken to assign these changes, their proper place in the wide spectrum of ocular morbidity in leprosy. 76.1% of eyes of Type I reaction and 89.7% of eyes with Type II reaction showed some ocular involvement. Corneal hypoaesthesia, superficial punctate keratitis, a decrease of corneal film break up time (BUT), prominent corneal nerves, pigment on the endothelium of the cornea and a pigmented trabecular meshwork were the common ocular findings. The incidence of iridocyclitis in Type II reactions was low (8.1%). The significance of the ocular involvement in reactions in leprosy and the pathogenesis of iridocyclitis in Type II reactions is discussed.

Adolescent↗

Ciliary body melanocytoma with anterior segment pigment dispersion and elevated intraocular pressure.

PURPOSE: To discuss a case in which melanocytoma of the ciliary body presented with widespread pigment dispersion and elevated intraocular pressure (IOP). METHODS: A 64-year old woman presented with increased IOP and persistent anterior segment inflammation in her right eye. She had undergone a trabeculectomy for uncontrolled IOP before presentation. Slit-lamp examination, gonioscopy, and ultrasound biomicroscopy revealed a ciliary body mass with extension into the subconjunctiva in addition to widespread pigmentary dispersion in the anterior segment. Enucleation of the right eye was performed for histopathologic evaluation, as a diagnosis of ciliary body melanoma was made on clinical examination. RESULTS: Histopathologic findings were diagnostic of a melanocytoma of the ciliary body with necrosis and focal malignant transformation with extension of melanocytoma cells and melanophages into the subconjunctival space, trabecular meshwork, and anterior chamber angle. CONCLUSION: Melanocytoma of the ciliary body is a rare intraocular tumor that may present with pigment dispersion and secondary elevated IOP. Careful examination of the anterior segment is imperative in such cases.

Anterior Eye Segment↗

[Deep nonpenetrating sclerectomy and open angle glaucoma. Intermediate results from the first operated patients].

PURPOSE: The aim of this retropective study is to evaluate and to compare in glaucoma patients, the mid-term results of the non penetrating deep-sclerectomy (NPDS) with collagen implant or with per operative application of 5 fluorouracile (5 FU). MATERIAL AND METHODS: The aim of the NPDS, a new filtering surgical procedure, is to remove under a scleral flap the Schlemm's canal and the juxtacanalicular trabecular meshwork responsible for the outflow resistance in order to obtain a sub-conjunctival filtration of the aqueous humor with no opening of the anterior chamber. Forty-two open angle glaucoma patients with uncontrolled intra-ocular pressure and with no risk factor of bleb fibrosis, underwent a NPDS. In 27 eyes (group 1) a sponge soaked with 5 FU (50 mg/ml) was applied for 5 minutes in the scleral bed, and in 15 eyes (group-2) a collagen implant (Staar*) was sutured in the scleral bed. A complete ophthalmologic examination was performed on days 1, 8, months 1,2,3 and each 3 months until the end of the follow-up. In case of increased IOP, goniopuncture with the Nd: YAG laser was performed at any time of the post operative period. RESULTS: The mean intra-ocular pressure (IOP) significantly decreased from 23.5 +/- 5.1 mmHg to 15.5 +/- 2.9 at 11.1 +/- 5.6 months follow-up (group 1, p < 10(-3)) and from 22.6 +/- 6.9 Hg to 16.2 +/- 3.9 mmHg at 8.8, 3.6 months follow-up (group 2, p < 10(-3)) with a significant decrease in the medical treatment (p < 10(-3)). The Kaplan Meier probability of success (IOP < or = 20 mmHg without treatment and with no visual field deterioration) at 6 and 12 months was similar in both groups: 57.3% (group 1) and 66.0% (group 2) with a mean decrease in IOP of 30%. Goniopuncture had to be performed in more than one third of case in each group and was effective to control the IOP in half of the cases. No complication related to hypotony or inflammation occured in the post operative period. CONCLUSION: NPDS is an interesting alternative to the classical trabeculectomy since the post operative complications are markedly reduced. However, the mid-term control in IOP appears to be slightly lower. The use of a collagen device does not lead to better control in IOP as compared to the use of a sponge of 5 FU.

Administration, Topical↗

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.

Adult↗

Effects of ethacrynic acid on Schlemm's canal inner wall and outflow facility in human eyes.

PURPOSE: The role of the inner wall of Schlemm's canal in determining aqueous outflow facility is poorly understood. To quantify the relationship between inner wall pore characteristics and aqueous outflow facility in human eyes, both control eyes and eyes in which facility had been pharmacologically increased by ethacrynic acid (ECA) infusion were studied. METHODS: Outflow facility was measured in enucleated human eyes before and after delivery of 0.25 mM ECA (one eye of each of 6 pairs) or 2.5 mM ECA (one eye of each of 13 pairs). ECA, and vehicle in contralateral eyes, was delivered into Schlemm's canal by retroperfusion, thereby largely avoiding drug exposure to the trabecular meshwork. After facility measurement, eyes were fixed under conditions of either constant pressure (physiological intraocular pressure, 13 pairs) or "equal flow" (6 pairs) and were microdissected to expose the inner wall of Schlemm's canal. The density and diameter of intercellular and intracellular inner wall pores were measured using scanning electron microscopy. RESULTS: Retroperfusion with 2.5 mM ECA increased facility by 73% (P < 0.001), whereas 0.25 mM ECA increased facility by 19% (not statistically significant). The density of intercellular pores in the inner wall of Schlemm's canal was increased by 520% in 2.5 mM ECA-retroperfused eyes (P < 0.00004), whereas intracellular pore density remained approximately constant. Large pores (size > or = 1.1 microm) were particularly enhanced in ECA retroperfused eyes. The net change in facility due to ECA was not correlated with changes in pore density or other inner wall pore statistics. CONCLUSIONS: Our data are most consistent with a model in which pores in the inner wall of Schlemm's canal indirectly influence facility. However, measured changes in facility due to changes in inner wall properties did not agree with quantitative predictions of the pore funneling theory, suggesting that changes in facility may instead be due to gel leakage from the extracellular spaces of the juxtacanalicular tissue. More definitive experiments are required to confirm this hypothesis.

Adult↗