Immunosenescence, Prostate health, and Reverse glaucomaSeptember 2017
Glaucoma and its association with obstructive sleep apnea: A narrative review.
SA) is one of the systemic risk factors for glaucoma which causes irreversible visual field (VF) damage. We reviewed the published data of all types of studies on the association between these two conditions and papers regarding functional and structural changes related to glaucomatous damage using Scopus, web of science, and PubMed databases. There is evidence that the prevalence of glaucoma is higher in OSA patients, which independent of intraocular pressure (IOP). Studies have reported thinning of retinal nerve fiber layer (RNFL), alteration of optic nerve head, choroidal and macular thickness, and reduced VF sensitivity in patients of OSA with no history glaucoma. A negative correlation of apnea-hypopnea index with RNFL and VF indices has been described in some studies. Raised IOP was noted which is possibly related to obesity, supine position during sleep, and raised intracranial pressure. Diurnal fluctuations of IOP show more variations in OSA patients before and after continuous positive airway pressure (CPAP) therapy when compared with the normal cases. The vascular factors behind the pathogenesis include recurrent hypoxia with increased vascular resistance, oxidative stress damage to the optic nerve. In conclusion, comprehensive glaucoma evaluation should be recommended in patients with OSA and should also periodically monitor IOP during CPAP treatment which may trigger the progression of glaucomatous damage.
Oman J Ophthalmol. 2016 Sep-Dec;9(3): 125-134
Genetics and genetic testing for glaucoma.
PURPOSE OF REVIEW: In recent decades, investigators have identified numerous genes and genetic factors that cause or contribute risk for glaucoma. These findings have increased our understanding of disease mechanisms, provided us with new diagnostic tools, and may allow for development of improved therapies for glaucoma. However, genetic testing is most useful when it is reserved for appropriate patients. The purpose of this article is to review key points and recent developments regarding the genetics and genetic testing for glaucoma and to provide recommendations for when genetic testing may be warranted. RECENT FINDINGS: Large genome-wide association studies have identified multiple new susceptibility loci associated with primary open angle glaucoma and primary angle closure glaucoma. SUMMARY: Several glaucoma-causing genes and genetic risk factors for glaucoma have been discovered. As a result, there are specific clinical scenarios in which genetic testing is warranted. In select cases (i.e., familial juvenile open angle glaucoma), genetic testing can serve as a powerful tool to improve diagnostic accuracy, efficiency of disease surveillance, and selection of treatment, enabling physicians to better optimize care for their patients.
Curr Opin Ophthalmol. 2017 Mar;28(2):133-138
Presence and Risk Factors for Glaucoma in Patients with Diabetes.
Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure-the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients.
Curr Diab Rep. 2016 Dec;16(12):124
Impact of Drugs on Glaucoma and Intraocular Pressure.
Purpose Systemic drugs may have unfavourable effects on intraocular pressure, glaucoma and the efficacy of glaucoma drugs. Material and Methods The article provides a review of the literature from PubMed and clinical experience. Results Topical and systemic corticosteroids induce complex changes inside the trabecular meshwork. New genetic results improve the understanding of pathogenetic processes, although many questions are still open. Arterial hypertension and antihypertonic drugs may influence the risk of glaucoma, intraocular pressure and ocular perfusion pressure. Intravitreal anti-VEGF therapy may be associated with the risk of sustained intraocular pressure elevation. Systemic drugs with parasympaticolytic activity (e.g. psychopharmaceuticals) are able to induce acute angle block glaucoma. Conclusion New insights into the interactions between drugs (e.g. antihypertensives, corticosteroids) and glaucomatous optic neuropathy affect large patient groups and may improve understanding of the underlying pathogenetic processes in open angle glaucoma. There is a great need for further clinical and experimental research.
Klin Monbl Augenheilkd. 2017 Feb;234(2): 179-184
Configuration of the drainage angle, intraocular pressure, and optic disc cupping in subjects with chronic angle-closure glaucoma.
OBJECTIVE: To investigate the relationship between drainage angle configuration with untreated intraocular pressure (IOP) and optic disc cupping in subjects with chronic angle-closure glaucoma (CACG). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred seventy-five Asian subjects with CACG who participated in a randomized controlled trial that investigated the IOP-reducing effect of latanoprost and timolol. METHODS: Chronic angle-closure glaucoma was defined as the presence of glaucomatous optic neuropathy (with or without a visual field defect), an anterior chamber angle in which the pigmented trabecular meshwork was not visible for at least 180 degrees on gonioscopy, and evidence of peripheral anterior synechiae (PAS) in association with elevated IOP of 21 mmHg or more. Static and dynamic gonioscopy were performed, the angles were graded in each quadrant according to the Shaffer scheme, and the number of clock hours of PAS was recorded. The untreated IOP and vertical cup-to-disc ratio were correlated with mean angle width and extent of PAS. MAIN OUTCOME MEASURES: Mean angle width, clock hours of PAS, IOP, and vertical cup-to-disc ratio. RESULTS: Most subjects were female (75%), and the mean age was 62.9+/-9.4 years. The mean angle width was 0.77+/-0.53 and the mean number of clock hours of PAS was 4.77+/-3.2 hours. Untreated IOP correlated with angle width (r = -0.23; P<0.001) and clock hours of PAS (r = 0.22; P<0.001). Vertical cup-to-disc ratio also correlated with angle width (r = -0.17; P = 0.004) and PAS (r = 0.28; P<0.001). Performing a multiple linear regression using baseline IOP as the outcome variable with age, gender, clock hours of PAS, and angle width as predictors, there was a 0.39-mmHg (95% confidence interval, 0.15-0.63) increase in baseline untreated IOP for each unit increase in clock hours of PAS (P = 0.002). CONCLUSIONS: In subjects with CACG, the e of the drainage angle were associated with higher untreated IOP and a larger vertical cup-to-disc ratio.
Ophthalmology. 2005 Jan;112(1):28-32
The progress in optic nerve regeneration, where are we?
Optic nerve regeneration is an important area of research. It can be used to treat patients suffering from optic neuropathy and provides insights into the treatment of numerous neurodegenerative diseases. There are many hurdles impeding optic regeneration in mammals. The mammalian central nervous system is non-permissive to regeneration and intrinsically lacks the capacity for axonal regrowth. Any axonal injury also triggers a vicious cycle of apoptosis. Understanding these hurdles provides us with a rough framework to appreciate the essential steps to bring about optic nerve regeneration: enhancing neuronal survival, axon regeneration, remyelination and establishing functional synapses to the original neuronal targets. In this review article, we will go through current potential treatments for optic nerve regeneration, which includes neurotrophic factor provision, inflammatory stimulation, growth inhibition suppression, intracellular signaling modification and modeling of bridging substrates.
Neural Regen Res. 2016 Jan;11(1):32-6
Disease progression and the need for neuroprotection in glaucoma management.
Glaucoma, the second leading cause of worldwide blindness, is a progressive optic neuropathy characterized by a loss of retinal ganglion cells and their axons beyond typical age-related baseline loss. Diagnosis is defined by optic disc and visual field changes, and the primary goal of glaucoma treatment is to preserve vision. Proven existing therapies (ie, pharmacotherapy, laser, and surgical) focus on reduction of intraocular pressure (IOP), although elevated IOP is no longer a diagnostic feature of glaucoma. New neuroprotectant drugs are being investigated, with the goal of reducing retinal ganglion cell loss, either prophylactically or after the insult has occurred. Various treatment strategies are being evaluated, and include a neuroprotectant only, or a complete therapy approach comprised of both a neuroprotectant supplemented by an IOP-lowering therapy. Dually targeted complete therapy may directly preserve the optic nerve, decrease the risk factors that cause glaucoma damage, and reduce glaucoma-related morbidities. Neuroprotectant therapy outcomes should include functional and structural effects of disease progression and neuroprotectant therapies, as well as patient functioning and economic impact.
Am J Manag Care. 2008 Feb;14(1 Suppl):S15-9
Neuroprotection in glaucoma - Is there a future role?
In glaucoma, the major cause of global irreversible blindness, there is an urgent need for treatment modalities that directly target the RGCs. The discovery of an alternative therapeutic approach, independent of IOP reduction, is highly sought after, due to the indirect nature and limited effectiveness of IOP lowering therapy in preventing RGC loss. Several mechanisms have been implicated in initiating the apoptotic cascade in glaucomatous retinopathy and numerous drugs have been shown to be neuroprotective in animal models of glaucoma. These mechanisms and their potential treatment include excitotoxicity, protein misfolding, mitochondrial dysfunction, oxidative stress, inflammation and neurotrophin deprivation. All of these mechanisms ultimately lead to programmed cell death with loss of RGCs. In this article we summarize the mechanisms involved in glaucomatous disease, highlight the rationale for neuroprotection in glaucoma management and review current potential neuroprotective strategies targeting RGCs from the laboratory to the clinic.
Exp Eye Res. 2010 Nov;91(5):554-66
Glaucoma is the second most common cause of legal blindness in the United States. Open-angle glaucoma is an asymptomatic, progressive optic neuropathy characterized by enlarging optic disc cupping and visual field loss. Patients at increased risk for open-angle glaucoma include blacks older than 40 years, whites older than 65 years, and persons with a family history of glaucoma or a personal history of diabetes or severe myopia. Elevated intraocular pressure is a strong, modifiable risk factor for open-angle glaucoma, but it is not diagnostic. Some patients with glaucoma have normal intraocular pressure (i.e., normal-pressure glaucoma), and many patients with elevated intraocular pressure do not have glaucoma (i.e., glaucoma suspects). Routine measurement of intraocular pressure by primary care physicians to screen patients for glaucoma is not recommended. Open-angle glaucoma usually is discovered during an adult eye evaluation performed for other indications. Final diagnosis and treatment occur in collaboration with ophthalmologists and optometrists. Formal visual field testing (perimetry) is a mainstay of glaucoma diagnosis and management. Eye drops, commonly nonspecific beta-blocker or prostaglandin analog drops, generally are the first-line treatment to reduce intraocular pressure. Laser treatment and surgery usually are reserved for patients in whom medical treatment has failed. Without treatment, open-angle glaucoma can end in irreversible vision loss.
Am Fam Physician. 2003 May 1;67(9):1937-44
Protective effects of bilberry (Vaccinium myrtillus L.) extract against endotoxin-induced uveitis in mice.
Endotoxin-induced uveitis (EIU), a useful animal model of ocular inflammation, is induced by injection of lipopolysacharide (LPS). These experiments showed that the nitric oxide (NO) level significantly increased in the whole eye homogenate of BALB/C mice 24 h after footpad injection of LPS at a dosage of 100 mg/mouse. However, the elevated NO level was significantly reduced by oral administration of bilberry extract (containing 42.04% anthocyanins) at dosages of 50, 100, and 200 mg/kg/day for 5 days before the LPS injection. In addition, bilberry extract decreased malondialdehyde (MDA) level and increased oxygen radical absorbance capacity (ORAC) level, glutathione (GSH) level, vitamin C level, and total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Moreover, bilberry extract increased expression of copper/zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and GPx mRNA. Taken together, bilberry extract showed protective effects against EIU, whereas the effects of bilberry extract (100 and 200 mg/kg/day, 5 days) were dose-dependent. In conclusion, these results provide new evidence to elucidate the beneficial effects of bilberry extract on eye health.
J Agric Food Chem. 2010 Apr 28;58(8):4731-6
Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.
PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively. RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation. CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.
Invest Ophthalmol Vis Sci. 2007 May;48(5): 343-9