Glaucoma and optic nerve repair

Glaucoma is a leading cause of irreversible blindness worldwide and causes progressive visual impairment attributable to the dysfunction and death of retinal ganglion cells (RGCs). Progression of visual field damage is slow and typically painless. Thus, glaucoma is often diagnosed after a substantial percentage of RGCs has been damaged. To date, clinical interventions are mainly restricted to the reduction of intraocular pressure (IOP), one of the major risk factors for this disease. However, the lowering of IOP is often insufficient to halt or reverse the progress of visual loss, underlining the need for the development of alternative treatment strategies. Several lines of evidence suggest that axonal damage of RGCs occurs primary at the optic nerve head, where axons appear to be most vulnerable. Axonal injury leads to the functional loss of RGCs and subsequently induces the death of the neurons. However, the detailed molecular mechanism(s) underlying IOP-induced optic nerve injury remain poorly understood. Moreover, whether glaucoma pathophysiology is primarily axonal, glial, or vascular remains unclear. Therefore, protective strategies to prevent further axonal and subsequent soma degeneration are of great importance to limit the progression of sight loss. In addition, strategies that stimulate injured RGCs to regenerate and reconnect axons with their central targets are necessary for functional restoration. The present review provides an overview of the context of glaucoma pathogenesis and surveys recent findings regarding potential strategies for axonal regeneration of RGCs and optic nerve repair, focusing on the role of cytokines and their downstream signaling pathways.     

Glaucoma in a patient with subclavian steal syndrome

Vascular disease may be an underlying factor in certain patients with normal tension glaucoma. Normal tension glaucoma patients with specific vascular and neurological symptoms, in correlation with results of clinical tests (i.e. intraocular pressure, ophthalmodynamometry, blood pressure), will benefit from a further work-up for systemic vascular disease. Subclavian steal syndrome is one such vascular disease which can produce symptoms and clinical signs which alert the clinician to evaluate the patient further. Subclavian steal syndrome can potentially decrease perfusion to the optic nerve head, making it more susceptible to glaucomatous cupping in the presence of normal intraocular pressures. The following case report illustrates a patient who developed subclavian steal syndrome and contralateral optic nerve head hypoperfusion.     

Early reduction of microglia activation by irradiation in a model of chronic glaucoma

Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.     

Selective laser trabeculoplasty in the treatment of pseudoexfoliation glaucoma in patients allergic to all anti-glaucoma drops

Secondary chronic open-angle glaucoma associated with pseudoexfoliation (PEX) syndrome accounts for approximately 25% of all glaucomas and represents the most common identifiable cause of glaucoma overall. Selective laser trabeculoplasty (SLT) is effective in reducing intraocular pressure (IOP) in glaucomatous patients and has the advantage of preserving surrounding structures. We report here SLT treatment of a 82 year old female with a secondary developed open-angle pseudoexfoliation glaucoma allergic to all anti glaucoma eye drops especially those which contain bensalconium chloridum as preservative. Since patient was allergic also to methyl-cellulose, we performed SLT with water as a mediator. Patient had PEX syndrome for 10 years, immature cataracts on both eyes, and best corrected visual acuity (BCVA) 0.7 on the right and 0.2 on the left eye. We have monitored intraocular pressure (IOP), the changes in the visual field and optic nerve. Preoperative IOP was 28 mmHg on the right and 30 mmHg on the left eye. The follow up period was 24 months with time points for measured parameters every 3 months. After 18 months IOP remained in the normal values (average 17 mmHg) on the right eye, but on the left eye it increased up to 28 mmHg. SLT re-treatment was carried out on the left eye and the IOP stabilized again on the values between 16-18mmHg. There were no significant change in the visual field and optic nerve configuration before and after SLT (C/D value for right eye: 0.3-0.4; C/D left eye: 0.5). Based on this case report, SLT seems to be very effective treatment for maintaining regular IOP in patient with PEX who is allergic to all types of medications.     

Ischemic tolerance protects the rat retina from glaucomatous damage

Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.     

Importance of circulating platelet aggregates and haemodynamic changes in ophthalmic artery and progression of visual field loss at pseudoexfoliation glaucoma

The aim of this work is to examine the role of circulating platelet aggregates (CPA) at pseudoexfoliation glaucoma (PXG), haemodynamic changes in the ophthalmic artery by ultrasonic color Doppler, searching for visual field progression. Vascular component at PXG and its role in VF progression dynamics has not been sufficiently explained, as well as CPA influence to ischaemic events related to optic nerve damage and VF progression. The examination included 80 patients, where of 35 (44%) men average age 68.3 +/- 7.0 and 45 (56%) women average age 65.7 +/- 7.0 (t = 1.66; p = 0.101). Forthy of them suffered from primary open angle glaucoma (POAG) as a control group (healthy), and 40 from pseudoexfoliative glaucoma (PXG) as an experimental group. All the examinees underwent complete ophthalmological examination: visual acuity, ocular fundus, intraocular pressure measured, anterior eye segment biomicroscopy with gonioscopy performed. Also VF examination was performed three times at 6 months intervals. Laboratory testing of CPA proportion values was performed by means of Wu an Hoak method and ultrasonic measurement of blood perfusion in the carotid tree, particularly concerning ophthalmic artery by means of color Doppler. Obtained decreased values of CPA proportion resulted in hypercoagulability of blood in PXG group. At PXG were also found increased blood flow resistivity indexes in ophthalmic artery (RI AO) and internal carotid artery (RI ACI), resulting with ischemia and hypoxia and finally progression of the visual filed damage. In conclusion, our study shows that examining CPA and ultrasonic monitoring of vascular parameters in ophthalmic artery with color Doppler may be the way of better understanding the vascular role in PXG prognosis.     

Analysis of the qualitative dermatoglyphics of the digito-palmar complex in patients with primary open angle glaucoma

The primary open-angle glaucomas are a group of diseases that have in common characteristic morphological changes at the optic nerve head and retinal nerve fiber layer, progressive retinal ganglion cells death and characteristic visual field loss. The risk for primary open angle glaucoma rises continuously with the level of the intraocular pressure. The disease advances slowly and there are no symptoms. Primary open angle glaucoma is caused by abnormal aqueous humour outflow in the trabecular meshwork in the open angle. Etiopathogenesis of primary open angle glaucoma is unclear. The increased risk of glaucoma in relatives has long been recognized. Frequency for manifestation of the disease is 10-30% in family members. The discovery of the specific gene loci responsible for the manifestation of glaucoma has helped us to understand its mechanism of origin and definitely confirmed the hereditary nature of this disease. Digito-palmar dermatoglyphs were already used to determine hereditary base of many diseases and it was the reason for investigation of their qualitative patterns in patients with glaucoma (22 males and 23 females), their immediate relatives (19 males and 23 females) in comparison to a group of phenotypically healthy population (52 males and 56 females). The results pointed a connection with the dermatoglyphic traits of the digito-palmar complex between patients with glaucoma and their immediate relatives. There is a possible discrimination of patients and their immediate relatives from phenotypically healthy population, too.     

A biomathematical model for pressure-dependent lamina cribrosa behavior.

Investigating the relationship between intraocular pressure and the behavior of the lamina cribrosa (the primary site of the optic nerve damage in glaucoma) is important to insight into the pathogenesis of glaucomatous optic neuropathy. In most previous studies, unsuitable approaches were used since the lamina cribrosa was not taken as the main target. In the present study, a linear model of elastic mechanics theory on the bending of thin circular plate was developed for this purpose. The structural features of the lamina cribrosa and the forces acting on the lamina cribrosa were analyzed, and the constitutive equation was formulated. The general solution on a class of Kármán Equation and the analytic solution on fixed boundary conditions were obtained, and from them, the morphological changes and the mechanical properties such as retrodisplacement and force distributions of the lamina cribrosa under pressure were derived. Some of the clinical phenomena occurring in glaucoma damage were explained with the results. Theoretical values were compared with the experimental data obtained by other investigators. The effects of structural parameters on susceptibilities to glaucoma damage were discussed. The biomathematical model, serving as formalistic expressions of the well-known hypothesis of pressure-dependent optic nerve damage in glaucoma, should make it possible for us to further understand and manage this disease.     

Structural and functional neuroprotection in glaucoma: role of galantamine-mediated activation of muscarinic acetylcholine receptors

Glaucoma is the leading cause of irreversible blindness worldwide. Loss of vision due to glaucoma is caused by the selective death of retinal ganglion cells (RGCs). Treatments for glaucoma, limited to drugs or surgery to lower intraocular pressure (IOP), are insufficient. Therefore, a pressing medical need exists for more effective therapies to prevent vision loss in glaucoma patients. In this in vivo study, we demonstrate that systemic administration of galantamine, an acetylcholinesterase inhibitor, promotes protection of RGC soma and axons in a rat glaucoma model. Functional deficits caused by high IOP, assessed by recording visual evoked potentials from the superior colliculus, were improved by galantamine. These effects were not related to a reduction in IOP because galantamine did not change the pressure in glaucomatous eyes and it promoted neuronal survival after optic nerve axotomy, a pressure-independent model of RGC death. Importantly, we demonstrate that galantamine-induced ganglion cell survival occurred by activation of types M1 and M4 muscarinic acetylcholine receptors, while nicotinic receptors were not involved. These data provide the first evidence of the clinical potential of galantamine as neuroprotectant for glaucoma and other optic neuropathies, and identify muscarinic receptors as potential therapeutic targets for preventing vision loss in these blinding diseases.     

Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma

Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.     

Oxidative and nitrative stress markers in glaucoma

Glaucoma is a progressive optic neuropathy and is the leading cause of blindness in the United States and other industrialized countries. Elevated pressure in the eye is a risk factor for glaucoma and indeed experimental studies of induced pressure elevation in nonhuman primate's results in typical glaucomatous optic nerve damage. However, normal intraocular pressure can also lead to loss of vision in glaucoma. Although the initiating causes leading to glaucoma are unknown, oxidative and nitrative stress appears to play a role in the progressive neuronal death that is characteristic of glaucomatous optic nerve damage. Increased markers of oxidative stress that have been reported in glaucoma include protein nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA bases. Studies have also highlighted the role of nitric oxide in glaucoma by reporting the presence of inducible nitric oxide synthase in the iris-ciliary body, retina and in the glaucomatous optic nerve head of experimental rat models. This review discusses the role of reactive oxygen and nitrogen species in the pathogenesis of glaucoma and examines the relevance of antioxidants in neurodegeneration associated with the disease. It is concluded that oxidative and nitrative stress have a pathogenic role in glaucoma.     

Modulation of mitochondria in the axon and soma of retinal ganglion cells in a rat glaucoma model

Mitochondrial abnormality has been implicated in various models of retinal ganglion cell (RGC) degeneration. We investigated modulation of mitochondrial membrane permeability and apoptosis-inducing factor (AIF) translocation in a rat experimental glaucoma model. A decrease in MitoTracker-labeled mitochondria around the lamina area of the optic nerve was observed in the glaucomatous eye. Immunoblot analysis for axonal motor proteins showed that a significant decrease in kinesin 1 and myosin Va levels in the glaucomatous optic nerve. A significant decrease in mitochondrial thioredoxin 2 (Trx2) level was observed in the optic nerve after intraocular pressure (IOP) elevation. Translocation of AIF from the mitochondria to the axoplasm and nucleus was observed in the axon and cell body, respectively. Trx2 over-expression in the mitochondrial membrane of RGC-5 cells inhibited AIF translocation, resulting in cytoprotective effect against neurotoxicity induced by TNF-α/buthionine sulfoximine treatment. In vivo transfection was performed with EGFP-Trx2 plasmid and electroporation. Over-expression of Trx2 in the retina and optic nerve indicated the protective effect against high IOP induced axonal degeneration. Thus, the decreased mitochondrial membrane potential and subsequent AIF translocation were involved in the glaucomatous neurodegeneration. Furthermore, modulation of mitochondria through the inhibition of AIF translocation may become a new treatment strategy for neurodegenerative disease, such as glaucoma.     

Apolipoprotein E-promoter single-nucleotide polymorphisms affect the phenotype of primary open-angle glaucoma and demonstrate interaction with the myocilin gene

Primary open-angle glaucoma (POAG) is an optic neuropathy that has a high worldwide prevalence and that shows strong evidence of complex inheritance. The myocilin (MYOC) gene is the only one that has thus far been shown to have mutations in patients with POAG. Apolipoprotein E (APOE) plays an essential role in lipid metabolism, and the APOE gene has been involved in neuronal degeneration that occurs in Alzheimer disease (AD). Here, we report that two APOE-promoter single-nucleotide polymorphisms (SNPs) previously associated with AD also modify the POAG phenotype. APOE(-219G) is associated with increased optic nerve damage, as reflected by increased cup:disk ratio and visual field alteration. In addition, APOE(-491T), interacting at a highly significant level with an SNP in the MYOC promoter, MYOC(-1000G), is associated with increased intraocular pressure (IOP) and with limited effectiveness of IOP-lowering treatments in patients with POAG. Together, these findings establish APOE as a potent modifier for POAG, which could explain the linkage to chromosome 19q previously observed by use of a genome scan for this condition and an increased frequency of glaucoma in patients with AD. The findings also shed new light on potential mechanisms of optic nerve damage and of IOP regulation in POAG.     

Immune maintenance in glaucoma: boosting the body’s own neuroprotective potential

Glaucoma, a slow progressive neurodegenerative disorder associated with death of retinal ganglion cells and degeneration of their connected optic nerve fibers, has been classically linked to high intraocular pressure. Regardless of the primary risk factor, degeneration may continue, resulting in further loss of neurons and subsequent glaucomatous damage. During the past decade, scientists and clinicians began to accept that, in addition or as an alternative to fighting off the primary risk factor(s), there is a need to protect the tissue from the ongoing spread of damage—an approach collectively termed “neuroprotection.” We found that the immune system, the body’s own defense mechanism, plays a key role in the ability of the optic nerve and the retina to withstand glaucomatous conditions. This defense involves recruitment of both innate and adaptive immune cells that together create a protective niche and thereby halt disease progression. The spontaneous immune response might not be sufficient, and therefore, we suggest boosting it by immunization (with the appropriate antigen, at specific timing and predetermined optimal dosing) which may be developed into a suitable therapeutic vaccination to treat glaucoma. This view of immune system involvement in glaucoma will raise new challenges in glaucoma research, changing the way in which clinicians perceive the disease and the approach to therapy.     

Erratum to: Immune maintenance in glaucoma: boosting the body’s own neuroprotective potential

Glaucoma, a slow progressive neurodegenerative disorder associated with death of retinal ganglion cells and degeneration of their connected optic nerve fibers, has been classically linked to high intraocular pressure. Regardless of the primary risk factor, degeneration may continue, resulting in further loss of neurons and subsequent glaucomatous damage. During the past decade, scientists and clinicians began to accept that, in addition or as an alternative to fighting off the primary risk factor(s), there is a need to protect the tissue from the ongoing spread of damage—an approach collectively termed “neuroprotection.” We found that the immune system, the body’s own defense mechanism, plays a key role in the ability of the optic nerve and the retina to withstand glaucomatous conditions. This defense involves recruitment of both innate and adaptive immune cells that together create a protective niche and thereby halt disease progression. The spontaneous immune response might not be sufficient, and therefore, we suggest boosting it by immunization (with the appropriate antigen, at specific timing and predetermined optimal dosing) which may be developed into a suitable therapeutic vaccination to treat glaucoma. This view of immune system involvement in glaucoma will raise new challenges in glaucoma research, changing the way in which clinicians perceive the disease and the approach to therapy.     

Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma

Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B)) receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B) receptors in the retina, mainly in retinal ganglion cells (RGCs), nerve fiber layer (NFL), and also in the inner plexiform layer (IPL) and inner nuclear layer (INL). To determine the role of ET(B) receptors in neurodegeneration, Wistar-Kyoto wild type (WT) and ET(B) receptor-deficient (KO) rats were subjected to retrograde labeling with Fluoro-Gold (FG), following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B) receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.     

Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage

In glaucoma, harmful intraocular pressure often contributes to retinal ganglion cell death. It is not clear, however, if intraocular pressure directly insults the retinal ganglion cell axon, the soma, or both. The pathways that mediate pressure-induced retinal ganglion cell death are poorly defined, and no molecules are known to be required. DBA/2J mice deficient in the proapoptotic molecule BCL2-associated X protein (BAX) were used to investigate the roles of BAX-mediated cell death pathways in glaucoma. Both Bax+/- and Bax-/- mice were protected from retinal ganglion cell death. In contrast, axonal degeneration was not prevented in either Bax+/- or Bax-/- mice. While BAX deficiency did not prevent axonal degeneration, it did slow axonal loss. Additionally, we compared the effects of BAX deficiency on the glaucoma to its effects on retinal ganglion cell death due to two insults that are proposed to participate in glaucoma. As in the glaucoma, BAX deficiency protected retinal ganglion cells after axon injury by optic nerve crush. However, it did not protect retinal ganglion cells from N-methyl-D-aspartate (NMDA)-induced excitotoxicity. BAX is required for retinal ganglion cell death in an inherited glaucoma; however, it is not required for retinal ganglion cell axon degeneration. This indicates that distinct somal and axonal degeneration pathways are active in this glaucoma. Finally, our data support a role for optic nerve injury but not for NMDA receptor-mediated excitotoxicity in this glaucoma. These findings indicate a need to understand axon-specific degeneration pathways in glaucoma, and they suggest that distinct somal and axonal degeneration pathways may need to be targeted to save vision.     

Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes

BackgroundProgressive disc tilting and the development or enlargement of peripapillary atrophy (PPA) are observed during a myopic shift in children. This could be related to the changes around the optic nerve head during eyeball elongation. If the biomechanical properties at or around the optic nerve head are changed after exposure to elevated intraocular pressure (IOP) in glaucoma eyes, different response of the disc tilting and PPA changes could take place during eyeball elongation by myopic shift. On the basis of this background, the aim of this study was to compare the morphological changes in the optic disc induced by a myopic shift during childhood between normal control eyes, eyes from disc suspects with an enlarged cup-to-disc ratio (CDR), and eyes with childhood glaucoma.MethodsTotal of 82 eyes from 82 subjects younger than 14 years of age were included in the study. Serial disc photographs were classified into one of two groups: eyes with an optic nerve head (ONH) or peripapillary atrophy (PPA) change or without an ONH/PPA change. Using ImageJ software, the outlines of the optic disc and PPA were plotted, and the vertical disc diameter (VDD), horizontal disc diameter (HDD), and maximum PPA width (PPW) were measured. The changes in the ratios of these parameters and the relationships between the degree of myopic shift or the ONH/PPA change were analyzed.ResultsTwenty-five eyes with normal optic disc appearance, 36 eyes with enlarged cup-to-disc ratio, and 21 eyes of glaucoma patients were analyzed. The initial intraocular pressure (IOP) at diagnosis was significantly different among the groups (P<0.001). The degree of myopic shift during follow-up period was not significantly different among the groups (P=0.612). However, the changes in the HDD/VDD and PPW/VDD ratios were significantly greater in the disc suspect group and significantly smaller in the glaucoma group. Among the 42 eyes with an ONH/PPA change, 16 (38.1%) were from the normal control group, 24 (57.1%) were from the disc suspect group, and 2 (4.8%) were from the glaucoma group (P < 0.001).

Conclusions and Relevance

The optic disc change during childhood myopic shift was different in eyes with various conditions. Eyes of childhood glaucoma showed less change in the disc morphology during myopic shift compared to eyes with normal disc or enlarged cup-to-disc ratio.     

Pseudoexfoliative syndrome and pseudoexfoliative glaucoma in Primorsko-Goranska County

The aim of this study is to evaluate pseudoexfoliative glaucoma (PEX) in Primorsko-Goranska County, Croatia, and its characteristics comparing to primary open angle glaucoma (POAG). In the study a hundred patients with open angle glaucoma were examined, twenty six of them had a pseudoexfoliative glaucoma diagnosed. We were following intraocular pressure (IOP) values, visual acuities, visual fields and optical nerve head changes retrospectively. Comparing to primary open angle glaucoma pseudoexfoliative glaucoma in Primorsko-Goranska County has less good prognosis because the IOP is usually higher and more difficult to control, we found progressive loss of retinal ganglion cells and visual field loss develop more rapidly. Because of that pseudoexfoliative glaucoma requires special treatment and following.     

Acquired pits of the optic nerve in glaucoma

An acquired pit of the optic nerve (APON) is a discrete, focal area of depression within the optic cup at the level of the lamina cribrosa. It is an under-diagnosed sign of glaucoma damage due to its subtle appearance. APONs occur more frequently unilaterally and in patients with normal-tension glaucoma (NTG). They often correspond to a deep, sharp-margined scotoma approaching or involving fixation. Given the location and progressive nature of the associated visual field defects, glaucoma patients and glaucoma suspects should be evaluated for this sign of localized optic nerve damage.