Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension.

Purpose: To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma. Methods: Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV. Results: Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP. Conclusions: Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.

Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts.

Glaucoma is a chronic optic neuropathy that leads to visual field loss. Elucidating the mechanisms underlying glaucoma is essential for developing new treatments, such as neuroprotective drugs. Various glaucoma models based on the induction of intraocular pressure (IOP) elevation have been established for use in glaucoma studies. However, the time-dependent pathological changes accompanying IOP elevation have not been fully elucidated. In this study, rat conjunctival fibroblasts were injected into the anterior chamber of rat eyes, and IOP elevation was induced for 28 days. Glaucomatous signs such as optic nerve head cupping, retinal thinning, glial activation and apoptotic signaling in the retina were obvious in the cell-injected eyes on the 14th day after injection. The pattern of retinal ganglion cell (RGC) loss differed by the magnitude of IOP elevation. The number of RGCs decreased by 37.5% in eyes with IOP lower than 50 mmHg (Under-50) and by 88.0% in those with IOP higher than 50 mmHg (Over-50) 28 days after cell injection. The RGC counts were correlated with IOP in the Under-50 group but not in the Over-50 group. Our model may contribute to the investigation of pathogenic mechanisms of glaucoma and the development of new glaucoma treatments.

Nanostructured lipid carriers for intraocular brimonidine localisation: development, in-vitro and in-vivo evaluation.

Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97 ± 1.98 nm, negative zeta potential (ZP) of -44.2 ± 7.81 mV, % entrapment efficiency (EE) of 83.631 ± 0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4 °C for 3 months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (-13.14 ± 1.28 mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.

Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

PURPOSE: Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration. METHODS: Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests. RESULTS: Adeno-associated virus-mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes. CONCLUSIONS: Adeno-associated virus-mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma.

Establishment of the ocular hypertension model using the common marmoset.

The purpose of this study was to establish an experimental glaucoma model in the common marmoset (Callithrix jacchus). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty twice at 2-week intervals in the left eyes of 4 common marmosets. IOP was measured before and at 4, 7, 8, 11, 13 weeks after first laser treatment, and ophthalmoscopic examinations were also performed. At 13 weeks after laser treatment, each eye was enucleated, and retinal cross-sections and optic nerve were prepared for histological examination. Mean IOP values measured at the above 5 time points were over 40 mmHg in laser-treated eyes in 3 marmosets, but IOP in one marmoset was transiently increased to 26.6 mmHg at 7 weeks and then declined to the baseline level. In ophthalmoscopy, deepened and enlarged optic disc cupping, depending on the extent of IOP elevation and duration, were observed in laser-treated eyes of 3 marmosets with persistent IOP elevation, but there was no apparent change in the optic disc in the laser-treated eye of one marmoset with transient IOP elevation. Histological examination showed marked atrophy with deepened and enlarged cupping of optic disc, thinning of retinal nerve fiber layer and retinal ganglion loss in the retina, and axonal atrophy and loss in the optic nerve, depending on the extent of IOP elevation and duration. In conclusion, we succeeded in producing an experimental glaucoma model in the common marmoset, and this model may be useful in elucidating the pathophysiological mechanism for glaucoma.

Protection of retinal ganglion cells and retinal vasculature by Lycium barbarum polysaccharides in a mouse model of acute ocular hypertension.

Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aß and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy.

Up-regulation of crystallins is involved in the neuroprotective effect of wolfberry on survival of retinal ganglion cells in rat ocular hypertension model.

Wolfberry (fruit of Lycium barbarum Linn) has been known for balancing 'Yin' and 'Yang' in the body, nourishing the liver and kidney, improving visual acuity for more than 2,500 years in oriental countries. The active components in wolfberry include L. barbarum polysaccharide (LBP), zeaxanthine, betaine, cerebroside and trace amounts of zinc, iron, and copper. Each of them confers distinct beneficial effects and together they help to explain widespread use of wolfberry in the eastern world. Earlier study reported the neuroprotective effects of LBP on retinal ganglion cell (RGC) in an experimental model of glaucoma and the underlying in vivo cellular mechanisms of LBP neuroprotection deserve further exploration. In this study, we adopted proteomics, functional genomics, to evaluate pharmacological effects of LBP on the neuronal survival pathways. Among the significantly changed proteins induced by LBP feeding on ocular hypertension (OH) retinas, only proteins in crystallin family were focused in this study. The proteomic results were further confirmed using the Western blotting of the retinas and immunohistochemical staining of the retinal sections. We demonstrated that neuroprotective effect of-wolfberry extract-LBP on the survival of RGCs may be mediated via direct up-regulation of neuronal survival signal betaB2-crystallin.

Reversal of optic disc cupping in glaucoma.

AIM: To study whether reversal of optic disc cupping after intraocular pressure (IOP) reduction is related to risk of glaucoma progression. METHODS: In this prospective follow-up study, where 51 patients with exfoliation glaucoma and five with ocular hypertension combined with exfoliation syndrome were followed for 6 years after IOP reduction, 24 showed progression of glaucoma in visual fields or optic nerve head (ONH) stereophotographs. ONH topography was measured with the Heidelberg Retina Tomograph (HRT). A decrease in HRT parameter cup volume of more than 5% was considered cup reversal. Multiple logistic regression was used to model progression of glaucoma. RESULTS: Cup reversal (OR 0.226; 95% CI 0.055 to 0.918, p = 0.037), final IOP (OR 1.216; 95% CI 1.000 to 1.479, p = 0.050) and visual field mean defect at entry (OR 1.158; 95% CI 1.034 to 1.296, p = 0.011) were associated with progression. IOP change from study entry to 6-year control visit was not associated with progression (OR 0.964, 95% CI 0.850 to 1.092, p = 0.56). CONCLUSION: Cup reversal seemed to be an independent protective factor for progression of glaucoma.

Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation.

OBJECTIVE: To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the myocilin mutation Thr377Met. METHOD AND DESIGN: Cross-sectional genetic study. Four unrelated pedigrees carrying the Thr377Met mutation were ascertained from more than 2000 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania and from families with glaucoma referred to the study from throughout Australia. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Thr377Met mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. RESULTS: From the 4 pedigrees carrying the Thr377Met mutation, 23 individuals with either ocular hypertension (OHT) or POAG were found, with a mean +/- SD age at diagnosis of 41.2 +/- 11.5 years, and a mean peak intraocular pressure of 31.7 +/- 9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of OHT or POAG (6 of these 9 were younger than 30 years). A single individual with POAG was identified who did not carry the Thr377Met mutation. For Thr377Met carriers, age-related penetrance for OHT or POAG was 88% at age 30 years. A positive family history of POAG was present for 3 of the 4 index cases. Thirteen (57%) of the 23 Thr377Met carriers with OHT or POAG had undergone glaucoma drainage surgery. Although the glaucoma in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. CONCLUSIONS: The GLC1A Thr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation. In addition, patients with glaucoma with the Thr377Met mutation were more likely to have undergone glaucoma drainage surgery.

Retinal ganglion cells recognized by serum autoantibody against gamma-enolase found in glaucoma patients.

PURPOSE: To study pathologic roles of the presence of serum autoantibodies against retinal ganglion cells in patients with glaucoma. METHODS: Serum autoantibody reactions were detected by Western blot analysis using retinal soluble fractions in 79 patients with glaucoma (normal-tension glaucoma [NTG], 23 cases; primary open-angle glaucoma [POAG], 56 cases) and 60 age-matched healthy subjects. Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and -negative patients. The retinal autoantigen recognized by patients' sera was identified by a combination of in-gel digestion and Edman sequencing. RESULTS: Western blot analysis revealed that serum autoantibody against retinal 50-kDa antigen was recognized in 20 out of 79 glaucoma patients (25.3%; 14 POAG and 6 NTG patients) and 60 age-matched control subjects (11.7%), respectively. Immunocytochemistry revealed that labeling of the ganglion cell layer (GCL) by IgG from glaucoma patients (POAG: 13/56, 23.2%; NTG: 6/23, 26%) existed at a significantly higher rate than that by IgG from control subjects (2/60, 3.3%; P < 0.05). In POAG, maximum IOP in the serum antibody positive-patients was significantly lower than that in the antibody-negative patients (P < 0.05). However, no statistical differences were observed in visual field loss, disc cupping, and other clinical factors between the antibody-positive and -negative groups in POAG and NTG. In-gel digestion of the 50-kDa band in two-dimensional polyacrylamide gels and Edman sequence analysis of the high-performance liquid chromatography-purified peptides identified the 50-kDa protein as gamma-enolase. Injection of the 50-kDa IgG from glaucoma patients or anti-gamma-enolase serum into the vitreous cavity of Lewis rats caused reduction of the b-wave of the electroretinogram and TdT-dUTP terminal nick-end labeling (TUNEL)-positive staining within the GCL. CONCLUSIONS: In the current study, serum autoantibody against 50-kDa protein identified as gamma-enolase in 25% of glaucoma patients.

Short-term effect of latanoprost and timolol eye drops on tear fluid and the ocular surface in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: To investigate and compare the short term effects of topical latanoprost and timolol on the tear fluid and ocular surface condition in patients with bilateral primary open angle glaucoma or ocular hypertension. METHODS: Thirty-seven patients were included in this randomized, double-masked, parallel group study. Patients received either latanoprost 0.005% (n= 18) or timolol 0.5% (n= 19) instilled once daily in the morning for a treatment period of 27 days. Routine ophthalmic examinations, including intraocular pressure measurement, as well as tests to evaluate tear fluid and the ocular surface were performed. RESULTS: After one drop of medication, tear secretion was significantly reduced by timolol, but not by latanoprost. At the end of the study the break-up time (BUT) was significantly decreased in the timolol group but not in the latanoprost group. The BUT still remained in the normal range in both groups, although it is important to note that timolol was administered at half the clinical dose. Both latanoprost and timolol tended to increase Rose-Bengal staining of the cornea and conjunctiva after one month of treatment but no statistically significant difference was found between the groups. Corneal sensitivity was within the normal range for all patients during the study. CONCLUSION: Regarding ocular surface effects, no clinically important differences between latanoprost and timolol were observed as all the effects remained in the normal range.

Association of ocular pressure and optic disc cup volume with red blood cell sodium-potassium ATPase inhibition.

PURPOSE: To determine if there were significant differences between the number of red blood cell ouabain binding sites in normals and untreated ocular hypertensives plus one open-angle glaucoma patient. METHODS: We measured the binding of (3)H ouabain to erythrocyte membranes of 23 normals, 25 ocular hypertensives and one open-angle glaucoma. We also measured the levels of plasma cortisol and digoxin in these subjects. Characteristics of cupping of the optic disc and thickness of the retinal nerve fiber layer, as well as area of optic disc pallor of these subjects were measured by stereophotogrammetry and by computerized image analysis from single and stereo photographs. RESULTS: The number of (3)H ouabain binding sites was observed to be significantly less in the ocular hypertensives and one glaucoma compared to the normals (p = 0.0009). In multi-variate analyses, to determine what other factors affected this difference, there was a significant negative association with mean intraocular pressure (p = 0.003) (average of both eyes) and total cup volume (average of both eyes) (p = 0.005), diagnosis of ocular hypertension and glaucoma (p = 0.0005) and male gender (p = 0.019). There was a significant positive association with plasma cortisol levels (p = 0.048), and diastolic blood pressure (p = 0.037). CONCLUSIONS: The number of (3)H ouabain binding sites in red blood cells decreases significantly with increasing ocular pressure and increasing cup volume indicating the possible presence of an increased systemic endogenous digoxin-like inhibitor and/or difference in the isozymes of Na(+), K(+)-ATPase which may be associated with increased levels of plasma cortisol in ocular hypertensives and glaucomas.

Confirmation of the rat model of chronic, moderately elevated intraocular pressure.

We have confirmed the usefulness of the rat model of chronic, moderately elevated intraocular pressure (IOP) for studying loss of retinal ganglion cells, and as a model for pharmacological neuroprotection studies that may be relevant to treating human glaucoma. By unilaterally cauterizing three episcleral vessels, as described previously in the literature by another laboratory, we observed an approximately 1.6-fold increase in IOP compared to the contralateral eye (18.6 vs 11.5 mm Hg, respectively). Elevated IOP persisted for 6 months without re-treatment. Cupping of the optic disk was observable by examination, in vivo. In 6 months, there was an approximately 40% loss of retinal ganglion cells in the peripheral retina. This model provides a reproducible and quantitative model for pharmacological experiments using neuroprotective agents.

Comparison of measurements of neuroretinal rim area between confocal laser scanning tomography and planimetry of photographs.

BACKGROUND: To compare neuroretinal rim area measurements by confocal scanning laser tomography and planimetric evaluation of optic disc photographs. METHODS: For 221 patients with primary and secondary open angle glaucoma, 72 subjects with ocular hypertension, and 139 normal subjects, the optic disc was morphometrically analysed by the confocal scanning laser tomograph HRT (Heidelberg retina tomograph) and by planimetric evaluation of stereo colour optic disc photographs. RESULTS: Absolute rim area and rim to disc area were significantly (p < 0.0001) larger with the HRT than with planimetric evaluation of photographs. Differences between the two methods were significantly (p < 0.01) larger in normal eyes with small cupping than in normal eyes with large cupping, and differences were significantly (p < 0.01) larger in glaucomatous eyes with marked nerve damage than in glaucomatous eyes with moderate nerve damage. Coefficients of correlations between rim measurements of both methods were R2 = 0.60 for rim to disc area and R2 = 0.33 for absolute rim area. Planimetric measurements of rim area correlated significantly (p < 0.05) better than HRT determinations of rim area with mean visual field defect and retinal nerve fibre layer visibility. CONCLUSIONS: Measurements of absolute rim area and rim to disc area are significantly larger with the HRT compared with planimetry of disc photographs. Differences between both methods depend on disc area, cup size and glaucoma stage. The reason may be that the HRT measures the retinal vessel trunk as part of the neuroretinal rim. The differences between both methods, which should be taken into account if disc measurements performed by both methods are compared with each other, may not influence the main advantage of the HRT--that is, morphological follow up examination of patients with glaucoma.

Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice.

PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.

[A study of neuroretinal rim morphology in physiologic large cups and early glaucoma].

OBJECTIVE: To find the differences of the physiologic large cups from the optic cup of early glaucoma. METHODS: The morphology of neuroretinal rim was studied. The subjects were divided into two groups: (1) 54 cases 88 eyes with physiologic large cups defined by cup/disk (C/D) ratio more than 0.6, optic disk areas more than 2.8 mm2, without neuroretinal rim loss within 3-6 years of follow-up, normal intraocular pressure and visual field. (2) 68 cases 89 eyes with early glaucoma defined by visual field defects, neuroretinal rim loss in follow-up and C/D ratio less than 0.8. The indexes of neuroretinal rim related to morphology are a series of rim widths and a parameter of cupping morphology which is a ratio of the vertical C/D over the horizontal C/D. RESULTS: The characteristics of a physiologic large cup are a large optic disk, a horizontal elliptic cupping and the widest neuroretinal rim at the inferior, followed by superior, nasal and temporal, while the characteristics of optic nerve head of glaucoma are normal size of optic disk, vertical elliptic cupping and the widest rim not at the inferior, since the inferior rim is subject to glaucomatous damage. CONCLUSION: To differentiate a physiologic large cup from a glaucomatous one, the most effective way is to apply the parameter of cupping morphology in combination with neuroretinal rim area and optic disk area in the multivariate discrimination.

Pattern electroretinogram and computerized optic nerve-head analysis in ocular hypertension--interim results after 2.5 years.

Evidence exists that both the pattern electroretinogram (PERG) as a parameter of ganglion-cell function and computerized morphometric disc analysis (ONHA) predict subsequent glaucomatous visual field defects in ocular hypertensive eyes. Since November 1991 we have conducted a prospective longitudinal study to evaluate the suitability of PERG and ONHA for detecting incipient glaucoma damage. Inclusion criteria were: an intraocular pressure of > or = 25 mmHG (at least two measurements taken on different days) or, in eyes with additional risk factors, > or = 23 mmHG; a normal Octopus visual field (mean defect < or = 2 dB, no local defect); and no definite glaucomatous disc cupping. After a mean follow-up period of 14.6 +/- 8.8 (range 1-33) months and with a mean intraocular pressure of 24.4 (range 18-42) mmHg, none of the 66 patients (115 eyes) converted to glaucoma. Furthermore, PERG and ONHA do not agree in their estimation of the glaucoma risk at this stage.

Decrease of optic disc cupping and pallor of ocular hypertensives with timolol therapy.

PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on optic disc cupping and pallor in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to placebo or 0.5% timolol drops to both eyes in a double masked clinical trial. Measurements of ocular pressure and photographs of the optic disc for cupping by photogrammetry and pallor by computerized image analysis were made at about 3 month intervals, for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol developed a significant decrease in ocular pressure and a significant decrease in optic disc cupping with a smaller decrease in pallor compared to subject treated with placebo. Multivariate analyses indicated that the decrease of optic disc cupping and pallor was not associated with the ocular pressure on treatment or the decrease in ocular pressure during the trial. CONCLUSION: Timolol treatment was associated with a decrease in optic disc cupping and pallor. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.

[3-dimensional topography of the optic papilla with laser scanning tomography: clinical correlation of cluster analysis]. / Dreidimensionale Papillentopographie mittels Laser Scanning Tomographie: Klinisches Korrelat einer Cluster-Analyse.

BACKGROUND The evaluation of optic disc topography is essential for the clinical diagnosis of primary open angle glaucoma. The purpose of this study was (1) to establish a computerized cluster formation of optic nerve head topography based on quantitative three-dimensional parameter values and (2) to describe the resulting clusters according to morphological appearance and visual fields. PATIENTS AND METHODS 337 optic nerve heads (glaucomatous optic neuropathy (n = 99), glaucoma suspects (n = 159), normals (n = 79) were analyzed using laser scanning tomography. A hierarchical cluster analysis was performed based on standardized variables (optic disc area, rim area, area-ratio, cup depth, cup steepness, height variations along the contour-line). Visual fields were tested by computerized static threshold perimetry. RESULTS A seven cluster solution met the optimizing criteria. The characteristic morphology of the clusters can be described as "normal" (N), "normal, large" (NL), "supernormal" (SN), "pseudonormal" (PN), "glaucoma-like-flat" (GF), "glaucoma-like-steep" (GS) and "macropapillary" (M). Visual fields were normal in 180 eyes. 99 eyes had glaucomatous field defects, 58 eyes revealed isolated relative scotomas < 10 db. Presence and degree of visual field defects varied within the automatically classified optic disc groups considerably. Visual field defects were found in 7.7% (SN), 8.3% (N), 18.8% (NL), 33.3% (M), 37% (PN), 64.7% (GF) and 83.3% (GS) respectively. Pseudonormal discs were characterized by a flattening of the height variations along the disc border. CONCLUSIONS (1) Optic nerve heads may be automatically classified based upon a combination of three-dimensional topographic variables. (2) Analysis of optic disc topography and computerized perimetry are supplementary tools in the evaluation of the glaucoma patient. Visual field defects may be present within any cluster. However, the likelyness of the presence of visual field defects differs considerably among the topometrically defined groups of optic nerve heads. Functional damage is to be expected in association with reduced height variations along the disc border, a small rim area and a steep cupping of the optic nerve head.