Glaucoma, the second leading cause of blindness worldwide is a neurodegenerative disease, with or without elevated ocular pressure, exhibiting several different phenotypic presentations, which result in progressive visual field loss after compromise of retinal ganglion cells and their axons to the optic nerve and brain. Predominant clinical glaucoma types are primary open angle, POAG, angle closure, and congenital; secondary glaucomas are: psuedoexfoliaiton, pigmentary, neovascular, traumatic, iridoendothelial, and uveitic glaucoma. In each of these types of glaucoma, genetic, epigenetic, proteomic, environmental, and mechanical forces may converge as well to cause or advance the disease. Alternatively, but not necessarily in an independent fashion, stress related pathways of oxidative stress, inflammation, infection, trauma, immune reaction, neuro-degeneration and mutant genomic products can produce deleterious misfolded proteins, antibodies, and aggregate deposits in the trabecular meshwork, TM, raise the intraocular pressure and result in optic nerve damage and loss of vision. Examining the interplay of these stress pathways with genetic, epigenetic, proteomic, environmental and mechanical forces to gain some understanding of molecular causes of glaucoma is the goal of this paper.

For over a decade VEGF (Vascular Endothelial Growth Factor) inhibitors have been the definitive treatment of choroidal neovascularization associated with adult onset macular degeneration. While the induction of “wet macular degeneration” treatment requires 2-3 intravitreal injections, over 2-3 months, the maintenance phase for sustained good visual acuity may be 6 injections or more per year, protracted over 6-8 years. Unfortunately, this treatment, even if the extended number and time of intravitreal injections could be packaged in a sustained delivery device, would still not represent a cure. Alternatively, if the treatment could be targeted to genetic, oxidative stress, inflammatory and immune modification from Bromodomain inhibitors (BRD I), (which would work through these transcription factors from an early stage to correct these macular problems), then patients might be given a more direct and shorter intervention with perhaps oral maintenance as necessary. Similar consideration for BRD I may be developed for uveitis, corneal scarring and retinal ganglion cell protection.

The global prevalence of AMD in 2020 is projected to be 196 million people [1] and that of Alzheimer’s disease was 50 million in 2017 [2]. Chronic oxidative stress and neuroinflammation from aging, injury, and individual risk factors (smoking, hypertension, arteriolosclerosis, obesity, dietary indiscretion, chronic anticholinergic use, and latent infection) in AMD and AD contribute to toxic protein deposits, loss of homeostatic protein clearance, and progressive neurodegeneration [3-11].

The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the elderly.

INTRODUCTION:In order to develop a model for investigating the genes that contribute to retinal degeneration, we examined the early graded photochemical stress response in the adult zebrafish (Danio rerio) retina and investigated the role of an NMDA inhibitor, thiokynurenate.METHODS:Following intravitreal injection of rose bengal (6 or 12 mg/mL), light (37x10(3) or 83x10(3) lx) was directed onto the central retina with and without 400 nM thiokynurenate. Histologic and electron microscopic analysis was performed at 2 and 4 h and gene expression analysis was carried out at 2, 4 and 6 h.RESULTS:Light and electron microscopy demonstrated a graded photochemical response in photoreceptor, nuclear, and ganglion cell layer thickness. Increased vacuolation of the inner plexiform layer was also observed. The inhibitor produced a distinct lesion pattern. Cellular stress genes were elevated in low and high lesions, while some homeobox gene expression was reduced with thiokynurenate.DISCUSSION:The phenotypic and genetic changes observed from this model can serve as a basis for understanding the pathology of retinal oxidative and cellular stress. These changes may aid our understanding of aging and macular degeneration.

We prospectively compared dynamic contour tonometry (DCT) to Goldmann (GAT) and hand-held tonometry (HHT) in normal, ocular hypertension, and glaucoma populations. Both measurements were made on each patient within a 5-minute period during routine office exams over 4 months. While DCT is in good overall agreement with GAT and HTT, there is some systematic deviation at different pressure ranges in normal, ocular hypertension, and glaucoma populations.

Complete brain fixation can be achieved with transthoracic cardiac infusion without thoracotomy. Light and electron microscopy tissue sections reveal preservation of cytoplasmic and nuclear structure at all magnification levels. Punched samples were obtained from the fixed tissue specimens in precisely localized areas for study using electron microscopy. This perfusion fixation technique provides both faster tissue harvesting capability and higher quality tissue preservation, without the artifacts of brain swelling and ventricular dilation observed in direct cardiac perfusion. Acute, discrete change in brain tissue can be studied.

INTRODUCTION:The neuronal cell death that occurs after ischemia-induced cerebral infarction (stroke) contains elements of apoptosis and necrosis, an intermediary form of the two, and a distinct excitotoxic process. We previously developed a photochemical model of stroke in the rat. We have now adapted this model for use in the mouse. The present manuscript describes the mouse model.METHODS:Minimal beam intensity (0.1 W/cm(2)) cold white light (8 min exposure) was used to evoke discrete infarcts in the parietal lobes of 11 mice sensitized by the administration of fresh Rose Bengal (10 mg/kg by rapid iv infusion).RESULTS:At 2 h, five out of five mice and at 6 h, six out of six mice demonstrated light microscopic histologic features like those in the rat model. These included a superior ischemic zone with shrunken and pyknotic nuclei, a middle transition zone of edematous vacuolated neuropil but normal neurons with open chromatin and retained Nissl granules, and an inferior zone with normal neurons. There was widespread nuclear terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) in the superior infarct zone in 11/11 mice. However, in the edematous vacuolated transition zone, 11/11 mice had TUNEL positive and negative nuclei randomly mixed. Light microscopic analysis of that same transition zone showed no pyknosis or chromatin bodies in the TUNEL positive or negative cells.DISCUSSION:In mice, photoactivation of Rose Bengal evoked similar infarct and transition zone patterns found previously in rats, with TUNEL evidence of apoptotic and nonapoptotic events. Thus, it will be possible to use this model for further quantitative study of apoptotic and excitotoxic events in wild and transgenic mice.

Over the last two decades several studies have suggested the role of photothrombotic occlusion of cerebral microvessels using rose bengal, resulting in small strokes in rodents that resemble those in humans. This paper describes such a photothrombotic method of acute small stroke induction in rats with histopathologic and in vivo magnetic resonance imaging (MRI) observations from 3 to 6 h after irradiation, which is homologous to a human autopsy specimen. Utilizing 30 min of irradiation with minimal beam intensity (0.1 W/cm(2)) cold white light in conjunction with 20 mg of intravenous (iv) rose bengal as a rapid infusion, small infarcts were induced photochemically in the frontal lobes of six rats. The infarcts showed a consistent pattern on histologic and in vivo MR sections when examined within 7 h or less of irradiation. Both MRI and histologic sections were comprised of (a) a superior zone of infarcted neurons, (b) a middle curvilinear transition zone of edema on MRI and histologically vacuolated neuropil, and (c) an inferior zone of normal neurons. Shorter duration water-sensitive (T2)- and postgadolinium longer duration (T1)-weighted signal decay images both showed a curvilinear hyperintense transition zone of edema. The mean infarct and transition zone areas measured from the histologic sections were comparable to those measured on the MRI. The infarct model described above allows in vivo observations using MRI with the potential for use in testing putative neuroprotective agents. As demonstrated by a comparison with the histologic features of such infarcts in surgical and autopsy brain specimens, the model is relevant to acute human ischemic infarcts.

The objective of this study was to determine whether rates of eye disease among the elderly are higher for residents of nursing homes than for persons who reside elsewhere. Articles reporting the prevalence of eye disease in geriatric populations (classified as nursing home or non-nursing home) were identified through a Medline search and a search of articles’ bibliographies. Identified articles were reviewed, and the relevant data compared with prevalence rates obtained from 738 residents of two nursing homes in New York City. Each of the nursing home residents received an ocular examination upon admission that determined the presence or absence of four varieties of eye disease—i.e. cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. Demographic data were obtained through chart review. Results indicate that prevalence rates of eye disease found in geriatric nursing home populations are generally higher than those found in other geriatric populations. With the exception of the rates for diabetic retinopathy, the rates found in the combined nursing home population sampled in this study were much higher than those reported in any previous study. It is concluded that eye disease is a more serious problem for elderly residents of nursing homes than for the elderly who reside in the community. Possible reasons for this are discussed.

Adenoviral conjuctivitis is one of the most common causes of acute red eye. Other diagnostic considerations include herpes virus conjunctivitis, chlamydial conjunctivitis, allergic conjunctivitis, and various other less common infections. Careful history taking can help in identifying a viral cause. The presentation may range from a minor conjunctivitis resulting from an upper respiratory tract infection to a serious, debilitating epidemic keratoconjunctivitis. Local care and interventions to minimize transmission are the cornerstones of management. Infection is usually self-limiting. Warm soaks and artificial tear lubricants may relieve itching and burning. Patients should be instructed to avoid touching their eyes, wash hands often, use disposable towels, and avoid group activities for as long as an ocular discharge is present. Use of topical corticosteroids or antibacterial preparations can lead to complications, and injudicious use of topical corticosteroids may mask serious conditions that require other interventions.