Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma

The BCL-2 (B-cell lymphoma-2) family of proteins contributes to mitochondrial-based apoptosis in models of neurodegeneration, including glaucomatous optic neuropathy (glaucoma), which degrades the retinal ganglion cell (RGC) axonal projection to the visual brain. Glaucoma is commonly associated with increased sensitivity to intraocular pressure (IOP) and involves a proximal program that leads to RGC dendritic pruning and a distal program that underlies axonopathy in the optic projection. While genetic deletion of the Bcl2-associated X protein (Bax-/-) prolongs RGC body survival in models of glaucoma and optic nerve trauma, axonopathy persists, thus raising the question of whether dendrites and the RGC light response are protected. Here, we used an inducible model of glaucoma in Bax-/- mice to determine if Bax contributes to RGC dendritic degeneration. We performed whole-cell recordings and dye filling in RGCs signaling light onset (αON-Sustained) and offset (αOFF-Sustained). We recovered RGC dendritic morphologies by confocal microscopy and analyzed dendritic arbor complexity and size. Additionally, we assessed RGC axon function by measuring anterograde axon transport of cholera toxin subunit B to the superior colliculus and behavioral spatial frequency threshold (i.e., spatial acuity). We found 1 month of IOP elevation did not cause significant RGC death in either WT or Bax-/- retinas. However, IOP elevation reduced dendritic arbor complexity of WT αON-Sustained and αOFF-Sustained RGCs. In the absence of Bax, αON- and αOFF-Sustained RGC dendritic arbors remained intact following IOP elevation. In addition to dendrites, neuroprotection by Bax-/- generalized to αON-and αOFF-Sustained RGC light- and current-evoked responses. Both anterograde axon transport and spatial acuity declined during IOP elevation in WT and Bax-/- mice. Collectively, our results indicate Bax contributes to RGC dendritic degeneration and distinguishes the proximal and distal neurodegenerative programs involved during the progression of glaucoma.

Steroid glaucoma

Glucocorticosteroids are widely used in clinical and ophthalmic practice, but their unjustifi ed and uncontrollable use is unacceptable. Prescription of steroids has to be controlled strictly and the level of intraocular pressure must be diagnosed, because one of the signifi cant side eff ect of steroids is increased intraocular pressure level and, as a result, the development of glaucomatous optic neuropathy. This review deals with the pathogenesis of an increase in the level of intraocular pressure against various forms of glucocorticosteroids intake, describes the time and duration of their ocular-hypertensive eff ect. The available data on the features of the clinical picture of steroid glaucoma, depending on the routes of their entry, have been studied in detail. The tactics of treating patients with ocular hypertension or a proven case of steroid glaucoma are described.

A personalized approach to preclinical diagnosis and initial therapy of primary glaucoma based on a comprehensive structural and functional examination. A clinical case

The principles of personalized approach to early diagnosis and monitoring of primary glaucoma are shown by a clinical example. We analyzed the potentials of contemporary electrophysiological tests for preclinically diagnosing glaucoma optic neuropathy and monitoring drug treatment. For the first time, we demonstrated the experience of using a new fixed combination of brinzolamide + brimonidine by a clinical case from our practice. The test results confirm the hypotensive effect of the medication (IOP reduction by 36.2 %) so that it can be recommended for the treatment of patients with glaucomatous optic neuropathy and that combined with vascular pathology.

Ankle-brachial index and ocular diseases in a Russian population

Background To assess potential associations between the ankle-brachial blood pressure index (ABI) and ocular disorders. Methods In the population-based cross-sectional Russian Ural Eye and Medical Study including 5,899 (80.5%) out of 7328 eligible participants aged 40+ years, the participants underwent a series of ocular and medical examinations including measurement of ABI. Results Blood pressure measurements of both arms and ankles were available for 3187 (54.0%) individuals. The mean ABI was 1.26 ± 0.19 (median:1.20; range: 0.61, 2.20). In multivariate analysis, a higher ABI was associated with younger age (P < 0.001; non-standardized regression coefficient B: −0.001; 95% confidence interval (CI): −0.002, −0.001), female sex (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04), lower body mass index (P < 0.001; B: −0.004; 95% CI: −0.006, −0.003), lower waist-to-hip ratio (P = 0.01; B: −0.10; 95% CI: −0.17, −0.02), lower glucose serum concentration (P = 0.008; B: −0.005; 95% CI: −0.009, −0.001), lower prevalence of arterial hypertension (P < 0.001; B: −0.14; 95% CI: −0.16, −0.12), higher mean systolic blood pressure (P < 0.001; B: 0.003; 95% CI: 0.002, 0.003), and higher prevalence of any alcohol consumption (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04). In that multivariate model, prevalence of glaucoma (P = 0.67) as a whole, open-angle glaucoma (P = 0.86) and angle-closure glaucoma (P = 0.54), stage of glaucomatous optic neuropathy (P = 0.57), prevalence of age-related macular degeneration (P = 0.88), prevalence and stage of diabetic retinopathy (P = 0.30, and P = 0.29, respectively), nuclear cataract (P = 0.32, and P = 0.41, resp.), cortical cataract (P = 0.33, and P = 0.92, resp.), subcapsular cataract (P = 0.74 and P = 0.60, resp.), and pseudoexfoliation (P = 0.44 and P = 0.47, resp.), intraocular pressure (P = 0.52), axial length (P = 0.20), and peripapillary retinal nerve fibre layer thickness (P = 0.55) were not significantly associated with the ABI. Conclusions In this ethnically mixed population from Russia, none of the major ocular diseases was associated with ABI suggesting that subclinical atherosclerosis is not markedly associated with the aetiology of these ocular disorders.

Parapapillary atrophy in optic neuropathies: Histology and clinical relevance

Parapapillary atrophy is one of the parameters of the optic nerve head area which are assessed during the ophthalmoscopic examination particularly useful to characterize glaucomatous optic neuropathy. Optical coherence tomography evaluation provides high-resolution images of the optic nerve head and surrounding area, and can be used to study parapapillary atrophy. Different parapapillary atrophy zones were described depending on their histological features and research has been conducted to investigate the possible association between the presence and/ or size of parapapillary atrophy zones and several optic nerve disorders. In this review we discuss the histology and the clinical findings related to parapapillary atrophy in patients with glaucomatous optic neuropathy, non-glaucomatous optic neuropathies (e.g. arteritic and non-arteritic anterior ischemic optic neuropathies; suprasellar and parasellar tumors), and other ocular conditions (e.g. high myopia; age-related macular degeneration). Two different histologic classifications were identified. Parapapillary atrophy was demonstrated in glaucoma and glaucoma-like neuropathies, but not in other types of optic nerve disorders.

Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG).Design: Cross-sectional case series.Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA.Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I (“U” shape), 34% type II (“Y” shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045).Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

Association of peripheral anterior synechia, intraocular pressure, and glaucomatous optic neuropathy in primary angle-closure diseases

AIM: To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and glaucomatous optic neuropathy (GON) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). METHODS: Totally 355 eyes (238 PAC and 117 PACG) of 181 patients were included in this retrospective analysis of baseline data from a randomized clinical trial. All patients had undergone a comprehensive ophthalmic examination. The extent of PAS in clock hours as determined on gonioscopy was documented. The independent effect of the extent of PAS on IOP and the prevalence of GON were determined using multivariable generalized estimating equation (GEE) models. RESULTS: The frequency of GON increased with the extent of PAS and a higher IOP. PAS were more extensive (8 vs 1 clock hour, P<0.001) and IOP higher (28.01 vs 18.00 mm Hg, P<0.001) in PACG compared to PAC. The prevalence of GON among the PAS quartiles were 10.2% (PAS<0.5 clock hours), 16.9% (PAS≥0.5 and PAS<3 clock hours), 29.6% (PAS≥3 and PAS<7 clock hours), and 74.4% (PAS≥7 clock hours), respectively. After adjusting for IOP, age, gender, spherical equivalent, average Shaffer score and number of medications, the odds ratio (OR) for GON was 4.4 (95%CI: 1.5-13.0; P=0.007) with PAS≥3 clock hours and 13.8 (95%CI: 4.3-43.6; P<0.001) with PAS≥7 clock hours as compared to eyes with PAS<0.5 clock hours. The frequency of GON increased linearly with the extent of PAS. Extent of PAS was also associated with higher IOP. Eyes with both PAS≥6 clock hours and IOP≥21 mm Hg had the highest risk of GON compared to eyes with both PAS<6 clock hours and IOP<21 mm Hg (OR=18.0, 95%CI: 7.5-43.4; P<0.001). CONCLUSION: The extent of PAS in PAC and PACG is an important predictor of higher IOP and is linearly associated with GON independent of IOP, suggesting other factors related to PAS formation may be involved in the development of GON in PACG.

COMPARATIVE ANALYSIS OF TONOMETRY METHODS

The principles of glaucoma diagnostics are based on the triad of symptoms -the excess of IOP over the tolerant level, changes in the visual field, primarily in the Bjerrum zone, and also on glaucomatous excavation of the optic nerve head. It should be recognized that the IOP level is the only proven risk factor for the progression of glaucomatous optic nerve atrophy and, at the same time, the only factor that we can influence. That is why the determination of IOP is of great importance in diagnosis and is the basis for evaluating the effectiveness of glaucoma treatment.Keywords: IOP (intraocular pressure), tonometry, glaucoma, primary open-angle glaucoma, glaucomatous optic neuropathy, tonometer, pneumotonometer

The role of B vitamins in preventing the progression of glaucomatous optic neuropathy

The literature review discusses the role of vitamins (in particular, B vitamins) in maintaining neuroprotective and antioxidant properties of the retina in glaucomatous optic neuropathy, and presents the data from foreign research papers devoted to studying the positive influence of vitamins of this group on the condition of ganglion cells of the retina and axons of the optic nerve.