Cell adhesion glycoproteins in the human lamina cribrosa.

PURPOSE: The distribution of the cell adhesion glycoproteins, laminin, fibronectin, tenascin, vitronectin, thrombospondin, and entactin/nidogen, was examined in the human lamina cribrosa. METHODS: Frozen sections of the optic nerve head from 7 normal human elderly donors were stained by immunohistochemistry. RESULTS: All six glycoproteins were detected in this tissue. While laminin and entactin/nidogen were observed linearly, reflecting the localization of basement membranes, fibronectin was identified diffusely. Marked tenascin immunoreactivity was apparent in the lamina cribrosa, but little or no tenascin staining was detected in the sclera. Vitronectin showed a fine fibrillar staining pattern in the lamina cribrosa, and, to a lesser extent, in the sclera and pial septa. Thrombospondin staining was apparent only in the sclera and the lamina cribrosa, which traversed the optic nerve. CONCLUSIONS: These results indicate that extracellular matrix components in the lamina cribrosa differ from those in the sclera or pial septa. This study is the first report that the human lamina cribrosa includes vitronectin and thrombospondin.

Expression and localization of angiogenic inhibitory factor, chondromodulin-I, in adult rat eye.

PURPOSE: To determine the role in the eye of chondromodulin (ChM)-I, which has been identified in cartilage as an angiogenic inhibitor, the expression and localization and a possible function of ChM-I were investigated. METHODS: Expression and localization of ChM-I in rat eyes were examined by RNase protection assay and in situ hybridization and by immunostaining, using an antibody against a synthetic peptide. The effect of recombinant ChM-I on tube morphogenesis of retinal endothelial cells was examined in culture. RESULTS: The rat ChM-I gene was determined to encode the open reading frame of 334 amino acid residues, and ChM-I mRNA was exclusively expressed in cartilage, eye, and cerebellum in rats. ChM-I mRNA expression was evident in the iris-ciliary body, retina, and scleral compartments, but not in other compartments of the eye. In situ hybridization revealed mRNA expression in the ganglion cells, inner nuclear layer cells, and pigment epithelium in the retina and in the nonpigment epithelium of the ciliary body. Immunoreactive ChM-I was present in these cells and also in the vitreous body. Western blot analysis detected an approximately 25-kDa band of ChM-I presumed as a secretory form in the aqueous humor and vitreous body and an approximately 37-kDa band as a precursor form in the retina. Recombinant human ChM-I inhibited tube morphogenesis of human retinal endothelial cells in vitro. CONCLUSIONS: These observations indicate a potential role for ChM-I in inhibition of angiogenesis in the rat eye.

Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads.

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) in the optic nerve head in an experimentally induced glaucoma model. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after photocoagulation. The optic nerve head was examined for expression of TGF-beta1, -beta2 and -beta3 and PDGF-A and -B in frozen sections and by the biotin ExtraAvidin-alkali phosphatase method. RESULTS: Normal monkey eyes showed TGF-beta1, -beta2 and -beta3, and PDGF-A and -B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF-beta1 and -beta2 in the glial cells around the lamina cribrosa. The staining intensities for TGF-beta3, PDGF-A and -B were the same as in normal eyes. CONCLUSIONS: Eyes with experimental glaucoma showed higher expression of TGF-beta1 and -beta2 around the lamina cribrosa. These findings may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

Atomic force microscopy of intact and digested collagen molecules.

The present study was performed to analyse the structure of non-digested and digested collagen type I molecules by atomic force microscopy (AFM). Collagen type I molecules from the bovine skin were diluted with 0.05 N acetic acid, spread on a mica plate, air-dried and observed by non-contact mode AFM in air. Collagen molecules digested with Clostridium histolyticum collagenase were also examined by AFM. Intact collagen type I molecules were observed as twisted threads ranging mainly between 280 and 310 nm in length. The surface of the molecules was uneven and both ends usually slightly bulged like a globule. Depressions on the molecules were found throughout the length, and were most prominent approximately 70 nm from one end of the molecules. The collagenase-treated collagen molecules were degraded into fragments with various lengths, which corresponded to the data from sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The end of these fragments often appeared like a tuft, suggesting that the triple-helix unraveled at these regions.

[Collagen fibrils in nanophthalmic sclerae].

PURPOSE: To examine collagen fibrils in 3 nanophthalmos sclerae and to compare them with normal control sclerae morphometrically. MATERIALS AND METHODS: Three cases of nanophthalmos associated with uveal effusion were studied. When sclerectomy was performed, scleral specimens were collected and fixed with 3% glutaraldehyde/2.5% paraformaldehyde. After epon-embedding and ultrathin sectioning, they were examined by transmission electron microscopy. Collagen fibrils from both nanophthalmos and normal control sclerae were compared in diameters and numbers per micron 2 areas. RESULTS: All scleral tissues from the three cases were associated with irregularly woven and unclear collagen bundles. Several abnormal findings, such as twisting or fraying, were also detected in a few collagen fibrils. The diameter and density of normal-appearing collagen fibrils that occupied most areas of nanophthalmos sclerae were the same as those from normal control sclerae morphometrically. CONCLUSIONS: Although nanophthalmos sclerae even with uveal effusion showed thick irregular collagen bundles and a few abnormal collagen fibrils, most collagen fibrils appeared the same as normal controls.

Clinical Results of Selective Laser Trabeculoplasty.

Purpose: Selective laser trabeculoplasty (SLT) is a new technique aimed to developed to impact pigmented trabecular cells selectively. Compared with ordinary argon laser trabeculoplasty, it is expected to have fewer complications with more efficacy for open-angle glaucoma. In this study we performed SLT on 17 eyes of 10 patients with primary open-angle glaucoma and 1 eye with capsular glaucoma.Methods: Follow-up period was up to 10 months. Average energy irrachieted was 28.14 mJ (0.47 mJ x 59 spots) against pigmented trabecular band over the half circumference of anterior chamber angle.Results: Preoperative mean intraocular pressure (IOP) was 22.8 mmHg and postoperative mean IOP was decreased significantly to 8.6, 17.3, and 16.1 mmHg at 1, 3, and 6 months after treatment, respectively. The average maximum IOP reduction was 8.8 (3 approximately 1 8) mmHg after SLT. Among 11 eyes showing transient IOP elevation, 6 eyes had an elevation of more than 6 mmHg. No remarkable postoperative complications were noted.Conclusion: SLT is a safe and effective modality for the treatment of open-angle glaucoma such as primary open-angle glaucoma (POAG) and capsular glaucoma.

The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy.

The present study was designed to analyze the subfibrillar structure of corneal and scleral collagen fibrils by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Isolated collagen fibrils of the bovine cornea and sclera were fixed with 1% OsO4, stained with phosphotungstic acid and uranyl acetate, dehydrated in ethanol, critical point-dried, metal-coated, and observed in an in-lens type field emission SEM. Some isolated collagen fibrils were fixed with 1% OsO4, dehydrated, critical point-dried and observed without metal-coating in an AFM. Isolated collagen fibrils treated with acetic acid were also examined by SEM and AFM. SEM and AFM images revealed that corneal and scleral collagen fibrils had periodic transverse grooves and ridges on their surface; the periodicity (i.e., D-periodicity) was about 63 nm in the cornea and about 67 nm in the sclera. Both corneal and scleral collagen fibrils contained subfibrils running helicoidally in a rightward direction to the longitudinal axis of the fibril; the inclination angle was about 15 degrees in the corneal fibrils and 5 degrees in the scleral fibrils. These findings indicate that the different D-periodicity between corneal and scleral fibrils depends on the different inclinations of the subfibrils in each fibril. The present study thus showed that corneal collagen fibrils differ from scleral collagen fibrils not only in diameter but also in substructure.

Observation of human corneal and scleral collagen fibrils by atomic force microscopy

Purpose: We attempted to analyze the three-dimensional ultrastructure of human corneal and scleral collagen fibrils with an atomic force microscope (AFM).Methods: A normal eye removed from a 66-year-old male was used in the study. Suspended corneal and scleral collagen fibrils were individually attached to glass slides by centrifugation. These collagen fibrils were air-dried and observed with a noncontact mode AFM in air.Results: AFM imaging provided information on the surface topography of both corneal and scleral collagen fibrils. The corneal collagen fibrils had a height of 11.9 +/- 1.0 (mean +/- standard deviation) nm and the scleral fibrils of 82.5 +/- 35.6 nm. A periodic banding pattern of grooves and ridges was clearly found in both types of fibrils: the D-periodicity and the groove depth were 65.7 +/- 0.8 nm and 1.46 +/- 0.50 nm in the corneal fibrils, and 67.3 +/- 1.1 nm and 6.16 +/- 1. 23 nm in the scleral fibrils.Conclusions: Surface topographic images of human corneal and scleral collagen fibrils were clearly obtained with the AFM. This technique provides quantitative information on the surface morphology of the collagen fibrils at high resolution.

[Clinical results of selective laser trabeculoplasty].

PURPOSE: Selective laser trabeculoplasty (SLT) is a new technique aimed to developed to impact pigmented trabecular cells selectively. Compared with ordinary argon laser trabeculoplasty, it is expected to have fewer complications with more efficacy for open-angle glaucoma. In this study we performed SLT on 17 eyes of 10 patients with primary open-angle glaucoma and 1 eye with capsular glaucoma. METHODS: Follow-up period was up to 10 months. Average energy irrachieted was 28.14 mJ (0.47 mJ x 59 spots) against pigmented trabecular band over the half circumference of anterior chamber angle. RESULTS: Preoperative mean intraocular pressure (IOP) was 22.8 mmHg and postoperative mean IOP was decreased significantly to 8.6, 17.3, and 16.1 mmHg at 1, 3, and 6 months after treatment, respectively. The average maximum IOP reduction was 8.8 (3-18) mmHg after SLT. Among 11 eyes showing transient IOP elevation, 6 eyes had an elevation of more than 5 mmHg. No remarkable postoperative complications were noted. CONCLUSION: SLT is a safe and effective modality for the treatment of open-angle glaucoma such as primary open-angle glaucoma (POAG) and capsular glaucoma.

[Observation of human corneal and scleral collagen fibrils by atomic force microscopy].

PURPOSE: We attempted to analyze the three-dimensional ultrastructure of human corneal and scleral collagen fibrils with an atomic force microscope (AFM). METHODS: A normal eye removed from a 66-year-old male was used in the study. Suspended corneal and scleral collagen fibrils were individually attached to glass slides by centrifugation. These collagen fibrils were air-dried and observed with a non-contact mode AFM in air. RESULTS: AFM imaging provided information on the surface topography of both corneal and scleral collagen fibrils. The corneal collagen fibrils had a height of 11.9 +/- 1.0 (mean +/- standard deviation) nm and the scleral fibrils of 82.5 +/- 35.6 nm. A periodic banding pattern of grooves and ridges was clearly found in both types of fibrils; the D-periodicity and the groove depth were 65.7 +/- 0.8 nm and 1.46 +/- 0.50 nm in the corneal fibrils, and 67.3 +/- 1.1 nm and 6.16 +/- 1.23 nm in the scleral fibrils. CONCLUSIONS: Surface topographic images of human corneal and scleral collagen fibrils were clearly obtained with the AFM. This technique provides quantitative information on the surface morphology of the collagen fibrils at high resolution.

Treatment results of advanced neuroblastoma with the first Japanese study group protocol. Study Group of Japan for Treatment of Advanced Neuroblastoma.

PURPOSE: To elucidate the efficacy of intensive induction and consolidation chemotherapy regimens (Study Group of Japan for Advanced Neuroblastoma [JANB] 85) for patients with advanced neuroblastoma aged 1 year or older. PATIENT AND METHODS: One hundred fifty-seven patients with newly diagnosed advanced neuroblastoma were entered into this study between January 1985 and December 1990. Eligible patients were 12 months old or older with stage III or IV disease. The patients first received six cyclic courses of intensive induction chemotherapy (designated regimen A1) consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydro-pyranyl Adriamycin (pirarubicin; 40 mg/m2), and cisplatin (90 mg/m2). The patients were further treated with three different consolidation protocols: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea, dacarbazine, and bone marrow transplantation. RESULTS: Overall survival rates for patients with stage III disease without reference to the consolidation protocols were 80.8%, 76.9%, and 66.3% at 2, 5, and 10 years, respectively. The overall survival rates for patients with stage IV disease were 58.8%, 34.4%, and 28.9% at 2, 5, and 10 years, respectively. There were no statistically significant differences between the three consolidation treatment groups. Patients who did not achieve complete remission (CR) with induction chemotherapy and surgery all died, suggesting that CR is essential for the cure of advanced neuroblastoma. The overall 5-year survival rate of the 24 patients with N-myc amplified stage III and IV disease was 33.3%, and the longest survival time of a relapse-free patient was 103 months. CONCLUSION: The intensive induction chemotherapy regimen used in this study may be of significant value in increasing the CR rate and survival for patients with N-myc amplified and nonamplified advanced neuroblastoma.

Collagen fibrillar network in the optic nerve head of normal monkey eyes and monkey eyes with laser-induced glaucoma--a scanning electron microscopic study.

PURPOSE: To examine the three-dimensional organization of collagen fibrils in the lamina cribrosa of normal monkey eyes and monkey eyes with laser-induced glaucoma. METHODS: Intraocular pressure elevation and glaucomatous optic discs were obtained in one eye of three adult monkeys by repeated applications of argon laser to the chamber angle. The monkey eyes were enucleated, and the collagen fibrillar network was investigated by scanning electron microscopy after cell maceration with 10% sodium hydroxide and conductive staining. RESULTS: In normal monkey eyes, round to oval shaped regular laminar pores through which axon bundles exited were observed in the lamina cribrosa. The straight, column-like pores or openings were formed by multilayered laminar plates that aligned vertically in parallel with the optic nerves. The surface of the laminar plates was covered by delicate, loosely arranged collagen fibrils. The inner surface of the pores was smooth, made up of well-packed collagen fibers. In glaucomatous eyes, the laminar pores were clogged by tightened collagen fibrils. The inner surface of the pores was irregular, and the pores were narrowed or distorted. CONCLUSIONS: Alterations in the three-dimensional organization of collagen fibrils were demonstrated in the optic nerve head of glaucomatous monkey eyes. The architectural changes may affect the flexibility and resilience required of the lamina cribrosa in supporting optic nerve fibers.

Pupillary functions after cataract surgery using flexible iris retractor in patients with small pupil.

PURPOSE: To quantitatively assess pupillary functions after small pupil cataract surgery using the flexible iris retractor. METHODS: Subjects were 11 patients (12 eyes) with small pupils who underwent phacoemulsification and intraocular lens implantation. Pupils were enlarged using the flexible iris retractor intraoperatively, and postoperative iriscorder data were compared with the data of 20 normal controls who underwent standard phacoemulsification and intraocular lens implantation. RESULTS: Although pupillary area before light stimulus did not differ between the groups, contraction rate after light stimulus was significantly lower in the small pupil group than in the normal controls. The velocity of contraction and dilation was also significantly slower in the small pupil group. Wider pupillary stretching during surgery resulted in deteriorated pupillary functions after surgery. Eyes of patients on long-term miotic therapy with pilocarpine showed poorer pupillary reaction postoperatively. CONCLUSION: Inappropriate use of the flexible iris retractor causes an atonic, chronically enlarged postoperative pupil. To avoid postoperative pupillary complications, miotic pupils should not be stretched to larger than a 5.0 x 5.0 mm square.

[Changes in transforming growth factor-beta and platelet-derived growth factor in the optic nerve head in monkey experimental glaucoma].

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet derived growth factor (PDGF) in the optic nerve heads in experimentally induced glaucoma. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after treatment. The optic nerve head was examined for expression of TGF beta 1, beta 2, and beta 3, and PDGF A and B in frozen sections and by the biotin-ExtrAvidin-Alkali Phosphatase method. FINDINGS: Normal monkey eyes showed TGF beta 1, beta 2, and beta 3, and PDGF A, and B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF beta 1 and beta 2 in the glial cells around the lamina cribrosa. The staining intensities for TGF beta 3, PDGF A, and PDGF B were the same as in normal eyes. CONCLUSION: Eyes with experimental glaucoma showed higher expressions of TGF beta 1 and beta 2 around the lamina cribrosa. This finding may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

Three-dimensional appearance of Bowman's layer after radial keratotomy.

PURPOSE: To examine the 3-dimensional collagen fibrillar architecture of Bowman's layer after radial keratotomy (RK). SETTING: Department of Ophthalmology, Niigata University School of Medicine, Niigata, Japan. METHODS: This study used monkey eyes in which 0.3 mm deep radial incisions were made on the cornea 2 weeks and 1, 6, and 12 months before the animals were killed. Corneal buttons were immersed in a fixative and the cells macerated with sodium hydroxide 10%. Scanning electron microscopy (SEM) was performed according to standard procedures. A part of the specimens was embedded in epoxy resin for light microscopic (LM) observation for comparison. RESULTS: The 3-dimensional collagen fibrillar architecture of Bowman's layer was revealed by SEM. The rupture of Bowman's layer could be seen 12 months after surgery and there was no continuity of collagen fibrils in the ruptured area. In LM observations, the width of the stromal incisions gradually became narrower near 12 months after surgery. CONCLUSION: Our cell-maceration/SEM method showed that the rupture of Bowman's layer remained up to 12 months after RK. This suggests that discontinuity of Bowman's layer may be responsible for globe rupture after RK.

[Glaucoma with microcornea; morphometry and differential diagnosis].

To evaluate the characteristics of 10 glaucomatous cases with microcornea, we measured corneal diameter, curvature, axial length, and depth of anterior chamber, and examined the eyes with a specular microscope and an ultrasound biomicroscope. The ten cases examined in this study included 1 case of cornea plana, 2 cases of sclerocornea, 2 cases of nanophthalmos, and 5 cases of anterior microphthalmos. Three of the 10 cases were combined with open angle glaucoma, and the others with closed angle glaucoma. Open-angle glaucoma seemed like developmental glaucoma with angle maldevelopment. The closed angle type may appear at a younger age than in patients who have simple pupilary block. There are probably complex mechanisms related with closed angle glaucoma with microcornea. While differential diagnosis among these cases is relatively easy, we should evaluate how or why the intraocular pressure rises as far as possible before forming a treatment plan for each patient.

Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink.

A simple and reproducible rodent glaucoma model is required to elucidate the pathophysiology of damage to the optic nerve. We developed chronically elevated intraocular pressure (IOP) unilaterally in rats by injecting india ink into the anterior chamber of one eye using a 30-gauge needle. One week later, trapped carbon particles in the chamber angle formed a black band along the corneal limbus in the injected eyes. We performed direct laser photocoagulation without a gonio lens, and selectively burned the trabecular meshwork. Intraocular pressure was measured every week and laser photocoagulation was repeated until mean IOP in the experimental eyes rose above 25 mmHg. Unilateral IOP elevation was attained in all rats within 4 weeks. Twelve weeks after ink injection, we sacrificed the rats and excised the eyes for histologic analysis. The anterior chamber angle showed peripheral anterior synechia caused by laser photocoagulation, and carbon particles were engulfed by macrophages that infiltrated the ciliary cleft. In the optic nerve head, a remarkable decrease in the nerve fiber layer and cavernous degeneration were observed, suggesting glaucomatous optic nerve damage. This experimental rodent model should facilitate the study of the complex mechanisms involved in glaucoma.

Localization and expression of AQP5 in cornea, serous salivary glands, and pulmonary epithelial cells.

Aquaporin (AQP) 5 gene was recently isolated from salivary gland and identified as a member of the AQP family. The mRNA expression and localization have been examined in several organs. The present study was focused on elucidation of AQP5 expression and localization in the eye, salivary gland, and lung in rat. RNase protection assay confirmed intense expression of AQP5 mRNA in these organs but negligible expression in other organs. To examine the mRNA expression sites in the eye, several portions were microdissected for total RNA isolation. AQP5 mRNA was enriched in cornea but not in other portions (retina, lens, iris/ciliary body, conjunctiva, or sclera). AQP5 was selectively localized on the surface of corneal epithelium in the eye by immunohistochemistry and immunoelectron microscopy using an affinity-purified anti-AQP5 antibody. AQP5 was also localized on apical membranes of acinar cells in the lacrimal gland and on the microvilli protruding into intracellular secretory canaliculi of the serous salivary gland. In the lung, apical membranes of type I pulmonary epithelial cells were also immunostained with the antibody. These findings suggest a role of AQP5 in water transport to prevent dehydration or to secrete watery products in these tissues.

[Influences of trabeculectomy combined with the use of mitomycin C on corneal endothelial cells].

We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/- standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.

The relationship between deterioration and reversal of optic disc cupping in monkeys with chronic experimental high-pressure glaucoma.

PURPOSE: To investigate the correlation between the deterioration in optic disc cupping during the chronic elevation of intraocular pressure (IOP) and the reversal of cupping during a subsequent reduction in IOP in experimental glaucoma. METHODS: We examined changes in the vertical and horizontal cup to disc ratios, the rim area to disc area ratio, and the cup volume to disc area ratio in 11 monkey eyes with laser-induced glaucoma using computerized stereo-image analysis. Correlations between changes in disc parameters during a spontaneous IOP reduction and changes in disc parameters during a period of chronic IOP elevation from baseline before laser exposure (baseline) to before the IOP reduction (pre-IOP reduction) and during the period from baseline to after the reduction in IOP (post-IOP reduction) were determined by linear regression analysis. RESULTS: All disc parameters improved significantly during IOP reduction and deteriorated significantly during the periods from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction. The degree of reversal in disc parameters was correlated with the deterioration from baseline to the pre-IOP reduction and from baseline to the post-IOP reduction in the vertical cup to disc ratio (r = 0.68, P = 0.0218 and r = 0.97, P < 0.0001, respectively), the horizontal cup to disc ratio (r = 0.57, P = 0.0649 and r = 0.98, P < 0.0001, respectively), the rim area to disc area ratio (r = 0.68, P = 0.0227 and r = 0.98, P < 0.0001, respectively), and the cup volume to disc area ratio (r = 0.67, P = 0.0256 and r = 0.88, P = 0.0004, respectively). CONCLUSION: The degree of deterioration in cupping from baseline before the induction of glaucoma may be an important determinant of the degree of cupping reversal during subsequent reductions in IOP in primate glaucoma.