W. Morton Grant

Why do some people go blind from glaucoma

Retrospective analysis of patients blinded by glaucoma has revealed a need to educate patients to the significance of premonitory symptoms, to investigate a higher incidence of blindness from open-angle glaucoma among blacks than whites, and to define the goals of therapy in relation to presenting pathology. Responding to this third need, circumstances of patients followed for 20 to 40 years with extensive documentation relating to open-angle glaucoma were analyzed. Some eyes with normal discs and fields were found to tolerate a tension of 30 mm Hg for many years without need of treatment. But, when abnormalities ranging from early glaucomatous cupping to advanced visual field defects were present on initial evaluation, progressive loss of field tended to occur at lower tensions. It appears that the worse the initial condition of the eye, the lower the tension needs to be to prevent further loss or blindness.

Progressive low-tension glaucoma treatment to stop glaucomatous cupping and field loss when these progress despite normal intraocular pressure

Our thesis, inspired by the experience and teaching of Paul A. Chandler, is that after the optic discs have developed cupping and atrophy from elevated intraocular pressure they tend to become abnormally vulnerable and, in some cases, may continue to deteriorate even if the intraocular pressure is brought to the teens. At this stage they behave the same as in eyes with so-called low-tension glaucoma, which have developed progressive cupping and atrophy with pressures always in the teens. In either case, we find that the progression of cupping and field loss can be stopped by reducing the intraocular pressure to lower levels, preferably to 10 mm Hg or less. We have found that such low pressures are most reliably attained by surgery, using a special technique we call the shell tamponade filtration procedure, which involves the use of a glaucoma shell in conjunction with standard (full-thickness sclerostomy) filtration operations and certain specific operative and perioperative maneuvers. We present nine case reports illustrating our thesis. Glaucomatous cupping and loss of visual field were progressing relentlessly at normal pressures in each case. This progressive deterioration was shown to be arrested by reduction of the pressure to less than 12 mm Hg in 13 eyes.

Experimental perfusions through the anterior and vitreous chambers with possible relationships to malignant glaucoma.

Enucleated eyes were perfused alternately via the anterior and vitreous chambers. At low intraocular pressure (IOP), vitreous humor presented considerable resistance to forward flow of perfusion fluid in calf eyes, but not in human eyes. In human eyes when the perfusion pressure was increased to 60 mm Hg, the resistance to flow forward from the vitreous body increased, but became practically nil again when the IOP was decreased. At high pressure the volume of the vitreous body apparently increases and the anterior hyaloid membrane probably presses against the ciliary body, reducing the area of hyaloid membrane through which fluid can flow. Whether increased perfusion pressure can in some other manner change the permeability of human vitreous to resemble that of the calf remains unanswered. Our results suggest that factors other than, or in addition to, simple diversion of aqeous humor must be important in malignant glaucoma.

Serum Obstruction of Aqueous Outflow in Enucleated Eyes

We perfused enucleated human eyes via the anterior chamber by the constant pressure technique. Infusion of human serum into the anterior chamber of enucleated human eyes for 30 minutes at 23 mm Hg pressure induced a 42% decrease in facility of outflow, which was not relieved by irrigation of the anterior chamber with balanced salt solution or alpha-chymotrypsin. Diluted serum also reduced the facility of outflow. Measured in a glass viscometer, diluted serum had less viscosity than undiluted, but interfered with outflow from the eye more than anticipated on the basis of viscosity alone. When we used lens depression to induce tension on the iridocorneal angle to simulate the effects of contraction of the ciliary muscle, outflow facility increased in control eyes that had not been exposed to serum and in serum-perfused eyes. However, the partial obstruction to outflow that had been induced by serum persisted. Normal serum components may become adsorbed or entrapped in the aqueous outflow system so as to obstruct outflow, and this may result in secondary glaucoma in eyes with chronic uveitis.

Ghost Cells as a Cause of Glaucoma

Clinical and investigative evidence indicated a glaucoma caused mainly by degenerated red blood cells, or ghost cells. These ghost cells, with altered shape, color, and pliability, accumulated in the vitreous cavity after hemorrhage. Following disruption of the anterior hyaloid face, they passed into the anterior chamber and caused severe glaucoma. In the anterior chamber, the tiny, khakicolored cells, circulating slowly, were frequently mistaken for white blood cells. They covered the trabecular meshwork or filled the inferior angle with a pathognomonic khaki-colored layer. They were identified by phase-contrast microscopic examination of anterior chamber aspirates. The decreased pliability of these degenerated cells seemed to account for their inability to pass easily through the human trabecular meshwork and, therefore, to cause severe glaucoma.

Cyclocryotherapy of Chronic Open-Angle Glaucoma in Aphakic Eyes

Twenty-six eyes of 25 patients with chronic open-angle glaucoma and surgical aphakia with inadequate control of intraocular pressure (IOP) despite maximal medical treatment were treated with cyclocryotherapy, according to a prospective protocol and specific technique. (Neovascular and synechial glaucoma were excluded from this series.) In most cases topical medications were resumed after cyclocryotherapy. During follow-up of seven to 95 months (average, 46 months), IOP was reduced to 19 mm Hg or lower in 24 out of 26 eyes (92%). In two eyes, persistent decrease in visual acuity, unrelated to reduction of IOP, occurred after cyclocryotherapy. On the basis of the long-term benefits obtained by this procedure, we concluded that cyclocryotherapy should be considered the procedure of choice in the treatment of primary open-angle glaucoma in surgically aphakic eyes when pressure cannot be adequately reduced by maximally tolerated medical treatment.

Outflow facility studies in the perfused human ocular anterior segment.

We have recently developed a tissue model of the human aqueous outflow pathway involving placement of the eviscerated anterior corneoscleral shell, [with lens and uveal tissue removed but trabecular meshwork (TM) attached] onto a specialized perfusion apparatus. The TM and associated outflow tissues are perfused with culture medium at a physiologically-relevant perfusion pressure in a 5% CO2 environment at 37 degrees C. Under these conditions, the perfused outflow tissues are similar for several days, to the human and/or subhuman primate outflow system in vivo with regard to morphology as well as several functional parameters. Measured facility of outflow (0.271 +/- 0.018 microliters min-1 mmHg-1, n = 79) is similar to facility values obtained by tonography in living human beings. Moreover, outflow facility decreases in a linear fashion with increased perfusion pressure by 1.4% mmHg-1. Finally the removal of the TM results in a 41% decrease in measured outflow resistance. The ability to study viable human outflow tissue for at least several days and the opportunity to establish a model which serves as an alternative to animal testing, point to the potential importance of this technique in investigating the biology of the aqueous outflow system.

Optic Disc Cupping in Arteritic Anterior Ischemic Optic Neuropathy Resembles Glaucomatous Cupping

Five cases of anterior ischemic optic neuropathy secondary to biopsy-proven giant cell arteritis are presented. In each case, cupping of the optic disc, which closely resembled glaucomatous cupping, was observed in the affected eye. The presence of glaucoma was ruled out on the basis of normal intraocular pressures and normal tonographic measurements of facility of outflow. These cases indicate that arteritic ischemic optic neuropathy can result in optic disc cupping, which closely resembles glaucomatous cupping. The similarities in the appearance of cupping of these discs with that seen in eyes with glaucoma suggest that the pathogenesis of cupping in glaucoma and in arteritic ischemic optic neuropathy may share some common mechanisms.

Phenylephrine Provocative Testing In The Pigmentary Dispersion Syndrome

Forty-nine patients with bilateral pigmentary dispersion syndrome (abnormal accumulation of pigment in the anterior chamber, principally from the posterior layers of the iris), including 31 patients with pigmentary glaucoma, underwent 10% phenylephrine testing in one eye for evaluation of liberation of pigment floaters into the anterior chamber and the influence of phenylephrine on the intraocular pressure. Ten patients with pigmentary glaucoma developed a 3+ to 4+ pigment response, but only two demonstrated a pressure rise greater than 2 mm Hg. The highest pressure rise observed was 7 mm Hg. Nine patients with pigmentary dispersion syndrome but without glaucoma also developed a 3+ to 4+ pigment response, but none of these had a pressure rise. The incidence of pigment liberation was higher in older patients and in pigmentary glaucoma patients receiving topical antiglaucoma therapy at the time of testing. The extent of iris transillumination did not correlate with the grade of phenylephrine-induced pigment liberation. Two pigmentary glaucoma patients, who did not liberate pigment or have a pressure rise when tested with phenylephrine, did exhibit spontaneous or exercise-induced liberations of pigment into the anterior chamber, with marked rises of intraocular pressure and obstruction of aqueous outflow.

Facility of flow through the trabecular meshwork.

This report presents one further detail in the investigation of factors which are responsible for the resistance to outflow of aqueous humor from the eye. One portion of this study which has already been reported was concerned with tonographic determination of facility and rate of outflow of aqueous humor in patients *; another portion has been experimental, concerned with measurement of facility of outflow from enucleated eyes, both normal and glaucomatous.† It has been shown that the facility of outflow from enucleated eyes differs by only about 10% from that found in vivo by tonography. 4 Furthermore, the external two-thirds of the perilimbal sclera, with its included portions of the outflow channels, can be removed from enucleated normal human eyes without appreciably increasing the facility of outflow. 5 It has appeared from these findings that the principal anatomic resistance to flow is to be found in the immediate neighborhood of Schlemms