Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma.

Protein-altering variants that are protective against human disease provide in vivo validation of therapeutic targets. Here we use genotyping data from UK Biobank (n = 337,151 unrelated White British individuals) and FinnGen (n = 176,899) to conduct a search for protein-altering variants conferring lower intraocular pressure (IOP) and protection against glaucoma. Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (ß = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10-9 and 1.07 x 10-13 for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). In FinnGen, we identify an ANGPTL7 missense variant at a greater than 50-fold increased frequency in Finland compared with other populations (rs147660927, p.Arg220Cys, MAF Finland = 4.3%), which was genotyped in 6,537 glaucoma patients and 170,362 controls and is associated with a 29% lower glaucoma risk (P = 1.9 x 10-12 for all glaucoma types and also protection against its subtypes including exfoliation, primary open-angle, and primary angle-closure). We further find three rarer variants in UK Biobank, including a protein-truncating variant, which confer a strong composite lowering of IOP (P = 0.0012 and 0.24 for Goldman-correlated and corneal compensated IOP, respectively), suggesting the protective mechanism likely resides in the loss of interaction or function. Our results support inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma.

From bench to behaviour: The role of lifestyle factors on intraocular pressure, neuroprotection, and disease progression in glaucoma.

Current glaucoma management centres on intraocular pressure (IOP) reduction through pharmacological and surgical therapy. Despite broad interest in active management of glaucoma through lifestyle modifications, such recommendations have yet to be incorporated into standards of treatment. In this review, noteworthy preclinical studies and their translations in clinical populations are discussed to evaluate the roles of lifestyle factors in lowering IOP, offering neuroprotection, and/or slowing disease progression in those with open-angle glaucoma. Current literature suggests that aerobic exercise may be associated with neuroprotection and decreased disease progression. Mindfulness is associated with IOP reductions and neuroprotection. Caffeine is associated with mild, transient IOP elevations of uncertain significance. Nicotinamide supplementation is associated with neuroprotection and short-term visual function improvement. This review also highlights knowledge gaps regarding these factors and opportunities to strengthen our understanding of their role in glaucoma, including future preclinical studies that elucidate underlying mechanisms and clinical studies with additional functional endpoints and longer follow-up.

1α,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice.

BACKGROUND: Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). METHODS: DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. RESULTS: DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. CONCLUSIONS: 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.

Protection of retinal ganglion cells in glaucoma: Current status and future.

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.

Prophylactic anti-glaucoma therapy in dogs with primary glaucoma: A practitioner survey of current medical protocols.

AIM: To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians. METHODS: A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection. RESULTS: Responses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months. CONCLUSIONS: Data analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.

Influence of Trace Elements on Neurodegenerative Diseases of The Eye-The Glaucoma Model.

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells.

Optogenetic Stimulation of the Superior Colliculus Confers Retinal Neuroprotection in a Mouse Glaucoma Model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) in the eye, which ultimately results in visual impairment or even blindness. Because current therapies often fail to halt disease progression, there is an unmet need for novel neuroprotective therapies to support RGC survival. Various research lines suggest that visual target centers in the brain support RGC functioning and survival. Here, we explored whether increasing neuronal activity in one of these projection areas could improve survival of RGCs in a mouse glaucoma model. Prolonged activation of an important murine RGC target area, the superior colliculus (SC), was established via a novel optogenetic stimulation paradigm. By leveraging the unique channel kinetics of the stabilized step function opsin (SSFO), protracted stimulation of the SC was achieved with only a brief light pulse. SSFO-mediated collicular stimulation was confirmed by immunohistochemistry for the immediate-early gene c-Fos and behavioral tracking, which both demonstrated consistent neuronal activity upon repeated stimulation. Finally, the neuroprotective potential of optogenetic collicular stimulation was investigated in mice of either sex subjected to a glaucoma model and a 63% reduction in RGC loss was found. This work describes a new paradigm for optogenetic collicular stimulation and a first demonstration that increasing target neuron activity can increase survival of the projecting neurons.SIGNIFICANCE STATEMENT Despite glaucoma being a leading cause of blindness and visual impairment worldwide, no curative therapies exist. This study describes a novel paradigm to reduce retinal ganglion cell (RGC) degeneration underlying glaucoma. Building on previous observations that RGC survival is supported by the target neurons to which they project and using an innovative optogenetic approach, we increased neuronal activity in the mouse superior colliculus, a main projection target of rodent RGCs. This proved to be efficient in reducing RGC loss in a glaucoma model. Our findings establish a new optogenetic paradigm for target stimulation and encourage further exploration of the molecular signaling pathways mediating retrograde neuroprotective communication.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury. METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts. RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury. CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

[Laboratory predictors of glaucoma in patients with middle and old age - a tool to improve the quality of life (literature review).]

There are about 1,3 billion people worldwide with visual disorders such as cataract and glaucoma, the prevalence of which is significantly higher in elder persons. Eye diseases remain a global medical, social and economic problem, associated with both the progression of the disease up to blindness and the lack of pathogenetic therapy methods. Timely detection of pathology is secondary prevention of glaucoma. At present, a number of diagnostic techniques have been developed, including mainly instrumental techniques. Undoubtedly, laboratory indicators should be used as screening methods of early diagnosis. Today, a group of biomarkers with different degrees of sensitivity and specificity has been identified. However, these markers have some difficulty in indicating. Finding signs of glaucoma in complete blood count is an important task. Glaucoma is recognized as a systemic disease, which should be reflected in the change in morphofunctional properties of blood elements.

[Current State of Primary Neuroprotection in Glaucoma]. / Derzeitiger Stand zur primären Neuroprotektion beim Glaukom.

In view of the aging members of our society, there will be an increase in severe visual impairment and blindness, also due to glaucoma, in the coming years. Therapy options are limited to treat occurring symptoms. Currently, only a deceleration of the pathogenesis progression, but no cure, is available. Therefore, it is necessary to develop new therapeutic strategies to treat glaucoma adequately and effectively, thus improving the quality of life of those affected. One possible approach seems to be primary neuroprotection, which acts independently of an intraocular pressure reduction. There are indications that components of the immune system play a role in the context of the disease or the loss of retinal ganglion cells. Thus, evidence of an involvement of heat shock proteins, the complement system, but also, for example, microglial cells, were found. To this end, therapeutic modulation of these factors seems to be an interesting new target for neuroprotection. Studies in animal models have shown that an inhibition of the complement system or microglia leads to a protection. Modulation of heat shock proteins may enhance their protective properties or inhibit their destroying function to prevent glaucoma damage. These neuroprotective substances could expand the treatment options of glaucoma patients in the future.

[Secondary Neuroprotection in Glaucoma from Change in Lifestyle]. / Sekundäre Neuroprotektion beim Glaukom durch Lebensstiländerungen.

Glaucoma therapy usually includes lowering IOP, but a healthy lifestyle may also be recommended. We discuss how this can be defined and the underlying secondary neuroprotective mechanisms. One neuroprotective measure is to avoid common neurotoxic pollution like cigarette smoking, ethanol, methanol or lead. Nutrition should be rich in variety and prevent vitamin B12 and folate deficiency. Supernutrition may lead to the metabolic syndrome and increase IOP, arterial hypertension and serum steroid levels. The metabolic syndrome can also lead to decreased renal function, which can cause accumulation of neurotoxic substances in the blood. Enhanced physical activities is useful, as this burns calories and reduces caloric intake. In contrast to supernutrition, during starvation ketone bodies like acetone, acetoacetate and ß-hydroxybutyrate are synthesised. These are thought to have neuroprotective effects, due to the additional power supply to the mitochondria. Ketosis can also occur after increased intake of fatty acids - which is generally not recommended, due to the cardiovascular risks involved. In addition to burning calories, endurance sports can reduce fear and depression, and neurotrophins with neuroprotective effects are released. Genetically determined or acquired mitochondrial dysfunction can both play a role in glaucomatous optic nerve impairment. Therefore, knowledge of secondary neuroprotective mechanisms can help in giving patient professional advice to minimise risks and to restore homeostasis in optic nerve metabolism.

Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration.

The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a common intraocular pressure (IOP)-related optic neuropathy characterized by the degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve. NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific phosphodiesterase (PDE) activity. This pathway appears to play a role in both the regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and subsequent RGC degeneration. Here, we investigated whether potentiation of cGMP signaling could protect RGCs from glaucomatous degeneration. We administered the PDE5 inhibitor tadalafil orally (10 mg/kg/day) in murine models of two forms of glaucoma - primary open angle glaucoma (POAG; GC-1-/- mice) and primary angle-closure glaucoma (PACG; Microbead Occlusion Model) - and measured RGC viability at both the soma and axon level. To determine the direct effect of increased cGMP on RGCs in vitro, we treated axotomized whole retina and primary RGC cultures with the cGMP analogue 8-Br-cGMP. Tadalafil treatment increased plasma cGMP levels in both models, but did not alter IOP or mean arterial pressure. Nonetheless, tadalafil treatment prevented degeneration of RGC soma and axons in both disease models. Treatment of whole, axotomized retina and primary RGC cultures with 8-Br-cGMP markedly attenuated both necrotic and apoptotic cell death pathways in RGCs. Our findings suggest that enhancement of the NO-GC-1-cGMP pathway protects the RGC body and axon in murine models of POAG and PACG, and that enhanced signaling through this pathway may serve as a novel glaucoma treatment, acting independently of IOP.

Precision medicine to prevent glaucoma-related blindness.

PURPOSE OF REVIEW: Approximately 10% of patients become blind despite using evidence-based guidelines developed from clinical trials and epidemiology studies. Our purpose is to review opportunities to decrease glaucoma-related blindness using the emerging principles of precision medicine. RECENT FINDINGS: The current review focuses on three topics: first, candidate biomarkers for angle-based surgeries, second, head-mounted display (HMD) technology for vision and testing, and third, glaucoma risk alleles discovered by genome-wide association studies. First, in angle-based surgeries, tracers injected into the anterior chamber or Schlemm's canal have allowed visualization of aqueous veins. We describe an innovative use of optical coherence tomography angiography to visualize aqueous veins in a case with 6-year successful outcome following catheter-based trabeculotomy. Second, HMD technology can augment perceived vision and can be used for perimetry testing. Third, developing genetic risk scores that characterize patients who are at highest risk for blindness is a priority. Such biomarker risk scores will integrate genome-wide association study-based risk alleles for glaucoma along with well known demographic and clinical risk factors. SUMMARY: As we gain more knowledge, precision medicine will enable clinicians to decrease glaucoma-related blindness by providing more timely interventions to those patients who are at highest risk for progression to blindness. VIDEO ABSTRACT: http://links.lww.com/COOP/A29.

Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma.

PURPOSE: Glaucoma is a common chronic neurodegenerative disease, which could lead to visual loss. In this study, we aimed to investigate whether fisetin, a natural flavone with anti-inflammatory and antioxidant properties, is able to alleviate glaucoma. METHODS: We employed a DBA/2J mouse model which was treated with or without fisetin. Pattern electroretinogram (P-ERG), visual evoked potentials (VEPs) and intraocular pressure (IOP) were evaluated. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression levels of TNF-α, IL-1ß and IL-6. Western blotting was performed to assess the activation of nuclear factor kappa-B (NF-κB). RESULTS: We found that DBA/2J mice treated with fisetin (10-30 mg/kg) showed improved P-ERG and VEP amplitudes and reduced IOP compared to untreated DBA/2J mice. In addition, there were more survived retinal ganglion cells (RGCs) and less activated microglia in fisetin-treated DBA/2J mice than those in untreated mice. Furthermore, secreted protein levels and mRNA levels of TNF-α, IL-1ß and IL-6 were significantly repressed by fisetin. The phosphorylated p65 level in the nucleus was dramatically reduced in fisetin-treated mice compared to it in untreated mice. Our results demonstrate that fisetin may exert its function through regulating cytokine productions and inhibiting NF-κB activation in the retina. CONCLUSION: In conclusion, fisetin is able to promote the visual functions of DBA/2J mice by inhibiting NF-κB activation.

Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model.

To investigate the neuroprotective effects of the mitochondria-targeted antioxidant Szeto-Schiller peptide 31 (SS-31) in a rat experimental glaucoma model, SS-31 was intraperitoneally (IP) injected into Sprague-Dawley rats, followed by intracameral injection of polystyrene microspheres to induce elevated intraocular pressure (IOP). After 6 weeks, electroretinography (ERG) and flash visual-evoked potentials (F-VEPs) were recorded to assess retinal function. Hematoxylin-eosin staining was performed on retinal cross-sections to measure ganglion cell complex (GCC) thickness. Apoptotic retinal cells were assessed by TUNEL staining. Brn3a-positive retinal ganglion cells (RGCs) were counted in retinal flat mounts via immunofluorescence. The retinal total SOD, SOD2, and MDA expression levels were assessed in retinal tissue homogenates. The cyt c, Bax, and Bcl-2 protein levels in rat retinas were detected by western blot analysis. Bax and Bcl-2 expressions were also evaluated using immunohistochemistry in paraffinized sections. Our results showed that the rats that received microsphere injection developed elevated IOP. SS-31 ameliorated the reductions in the a- and b-wave amplitudes on ERG and the F-VEP amplitude in glaucomatous eyes. GCC thickness was preserved, TUNEL-positive cells were decreased in the retina, and Brn3a-positive RGCs were increased in the SS-31-treated glaucoma group compared with those in the non-treated glaucoma group. SS-31 significantly reduced MDA levels and increased SOD2 levels after glaucoma induction. Significant suppression of cyt c release, upregulation of Bcl-2, and downregulation of Bax were observed following SS-31 administration. In summary, SS-31 exerts neuroprotective effects in this experimental glaucoma model by inhibiting mitochondrial dysfunction and therefore represents a promising therapeutic agent for glaucoma.

Effect of immediate postoperative intracameral tissue plasminogen activator (tPA) on anterior chamber fibrin formation in dogs undergoing phacoemulsification.

OBJECTIVE: To evaluate the postoperative effect of intracameral tPA (alteplase; Activase®, Genentech, San Francisco, CA), administered at immediate conclusion of phacoemulsification, on anterior chamber fibrin formation in dogs. PROCEDURES: Forty-one dogs (82 eyes) undergoing bilateral phacoemulsification received 25 µg/0.1 mL intracameral tPA in one eye and 0.1 mL unmedicated aqueous vehicle in the contralateral eye immediately after corneal incision closure. Intraocular pressure (IOP) was measured, and severity of anterior chamber fibrin formation, aqueous flare, pigment precipitates on the intraocular lens (IOL) implant, posterior capsular opacification (PCO), and corneal edema were graded at approximately 1 week, 2-3 weeks, 4-6 weeks, 8-12 weeks, and greater than 3 months postoperatively. RESULTS: Anterior chamber fibrin developed postoperatively in 68.3% of dogs (28/41) and 50% of eyes (41/82). In tPA-treated eyes, 53.7% (22/41) developed fibrin compared to 46.3% of control eyes (19/41). Some degree of postoperative ocular hypertension (POH) occurred in 53.7% of dogs (22/41) and 36.5% of eyes (30/82). In tPA-treated eyes, 34.1% (14/41) experienced POH compared to 39% of control eyes (16/41). Additional intracameral tPA injection was later required in 29.3% of both tPA-treated (12/41) and control eyes (12/41). CONCLUSIONS: Administration of intracameral tPA at immediate conclusion of canine phacoemulsification had no clinically observable effect on anterior chamber fibrin incidence at any time point. tPA-treated eyes showed no prophylaxis against POH or secondary glaucoma compared to control eyes and received late postoperative tPA injections at the same frequency as control eyes.

Effect of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on intraocular pressure in dogs.

PURPOSE: To measure IOP in animals, it is often necessary to use topical anesthetics. The use of these drugs may cause changes in IOP and interfere with the final results. To address this issue, the effects of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on IOP were investigated in ten adult dogs. METHODS: One drop of tetracaine was instilled in the right eye of half of the dogs and in the left eye of the other dogs; normal saline was instilled in the fellow eyes. The IOP in each dog was measured before and at 0, 5, 10, 15, 20, 25, 30, and 35 min after drug instillation using an electronic rebound tonometer. The effects of the other anesthetics were studied in the same way at intervals of at least 1 week. RESULTS: After instillation of tetracaine, the IOP decreased gradually, such that after 15 min, the IOP was significantly lower than the baseline (p = 0.022) and control values (p = 0.048). Proparacaine also reduced IOP after 10 min compared to baseline values (p = 0.046), but the two other drugs, bupivacaine and lidocaine, had no significant effect on IOP. The duration of eye anesthesia was 16, 20, 22, and 34 min for tetracaine, lidocaine, bupivacaine, and proparacaine, respectively. CONCLUSION: We recommend using drugs that combine inducing longer anesthesia with producing the smallest change in IOP, such as bupivacaine and, subsequently, lidocaine. Tetracaine and proparacaine have a significant effect on IOP, and if these drugs are used, this effect should be considered.

Descemet membrane endothelial keratoplasty and glaucoma.

PURPOSE OF REVIEW: The aim of this review is to describe the relationship between Descemet membrane endothelial keratoplasty (DMEK) and glaucoma. RECENT FINDINGS: Glaucoma after DMEK is a serious complication that may cause permanent visual loss, affect donor endothelial cells and graft survival. The mechanisms of raised intraocular pressure (IOP) after DMEK include reverse pupillary block in the early postoperative period, and steroid response in the late phase. The reduced risk of immunogenic graft rejection after DMEK necessitates a shorter duration of steroids, which may in turn reduce the risk of steroid response. On the other hand, eyes with preexisting glaucoma that undergo DMEK may have a poorer prognosis than those without glaucoma. SUMMARY: Early recognition and treatment of raised IOP is important after DMEK. Accurate IOP measurements after DMEK may be difficult to obtain because of the presence of an air bubble, corneal oedema, and corneal irregularities. A prophylactic peripheral iridectomy is recommended to prevent reverse pupillary block. Patients should posture face-up and be evaluated in the early postoperative period, as patients may be asymptomatic despite raised IOP. In order to reduce the risk of steroid response, weaker steroids may be prescribed after 1-3 months without adverse effects on DMEK outcomes.

Glaucoma Australia educational impact study: a randomized short-term clinical trial evaluating the association between glaucoma education and patient knowledge, anxiety and treatment satisfaction.

IMPORTANCE: Targeted education may impact glaucoma patients' clinical experience. BACKGROUND: The aim of this study was to measure the impact of patient-centred glaucoma-related education on knowledge, anxiety and treatment satisfaction. DESIGN: This was a multicentre Australia-wide randomized clinical trial. PARTICIPANTS: One hundred one newly diagnosed glaucoma patients were randomized 1:1 to intervention or control groups. METHODS: Those randomized to the Glaucoma Australia educational intervention received telephone-based counselling about glaucoma followed by mail-out information, in addition to usual care and information from their treating ophthalmologist. The control group received only usual care and information from their treating ophthalmologist. Surveys were administered at baseline and 4 weeks following intervention. MAIN OUTCOME MEASURES: The Auckland Glaucoma Knowledge Questionnaire measured glaucoma-related knowledge. The Hospital Anxiety and Depression Scale and Eye-Drop Satisfaction Questionnaire measured anxiety and patient treatment satisfaction, respectively. RESULTS: Mean age was 64.7 ± 11.1 years, and 52 (51.5%) were male. There was no noticeable increase in knowledge levels in the control group (mean difference: 0.04 logits, P = 0.7), compared with a 0.49-logit (P = 0.02) increase in knowledge levels in the intervention group. Between-group comparison showed a non-significant increase in knowledge (0.45 logits, P = 0.07) comparing intervention participants with controls. Intervention participants experienced a statistically significant decrease in anxiety compared to controls (-0.60 logits, P = 0.02). No between-group difference was found in Eye-Drop Satisfaction Questionnaire scores. CONCLUSIONS AND RELEVANCE: Patient-centred glaucoma-related education and support services may improve knowledge and can reduce anxiety for newly diagnosed glaucoma patients. All glaucoma patients should be adequately counselled about the nature of the disease and its management.