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Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness. The disease has conventionally been characterized by an elevated intraocular pressure (IOP); however, recent research has built the consensus that glaucoma is not only dependent on IOP but rather represents a multifactorial optic neuropathy. Although many risk factors have been identified ranging from demographics to co-morbidities to ocular structural predispositions, IOP is currently the only modifiable risk factor, most often treated by topical IOP-lowering medications. However, topical hypotensive regimens are prone to non-adherence and are largely inefficient, leading to disease progression in spite of treatment. As a result, several companies are developing sustained release (SR) drug delivery systems as alternatives to topical delivery to potentially overcome these barriers. Currently, Bimatoprost SR (DurystaTM) from Allergan plc is the only FDA-approved SR therapy for POAG. Other SR therapies under investigation include: bimatoprost ocular ring (Allergan) (ClinicalTrials.gov identifier: NCT01915940), iDose® (Glaukos Corporation) (NCT03519386), ENV515 (Envisia Therapeutics) (NCT02371746), OTX-TP (Ocular Therapeutix) (NCT02914509), OTX-TIC (Ocular Therapeutix) (NCT04060144), and latanoprost free acid SR (PolyActiva) (NCT04060758). Additionally, a wide variety of technologies for SR therapeutics are under investigation including ocular surface drug delivery systems such as contact lenses and nanotechnology. While challenges remain for SR drug delivery technology in POAG management, this technology may shift treatment paradigms and dramatically improve outcomes.

Purpose To evaluate the differences in structural parameters in patients with open-angle glaucoma (OAG), high myopia (M), and both diseases (OAG-M) concurrently. Methods 42 subjects with OAG (n = 14), M (n = 14) and OAG-M (n = 14) were included in a prospective pilot study. Mean peripapillary retinal nerve fiber layer (RNFL) thickness, RNFL in superior, temporal, inferior, nasal quadrants, macular ganglion cell complex (GCC) and its’ layers, vessel density (VD) of optic nerve head (ONH) and macula were evaluated. Results The OAG-M group showed significantly lowest thickness of mean peripapillary RNFL 89 (49–103) μm (p = 0.021), temporal quadrant 64.5 (51–109) μm (p = 0.001) and inferior quadrant 107 (64–124) μm (p = 0.025). The macular RNFL was thinnest in the OAG-M group (p Conclusions The M group showed the least thinning in the peripapillary RNFL thickness in the temporal quadrant and macular RNFL compared to other two groups. The highest macular VD in the inferior quadrant was in the M group in the superficial capillary plexus, deep capillary plexus and choriocapillaris. The M group showed highest VD in the temporal quadrant and in total VD of ONH at the superficial capillary plexus and in total VD of ONH at the deep capillary plexus. Practical recommendations The observed decrease in peripapillary RNFL thickness of the temporal quadrant, macular RNFL thickness, the decrease of macular VD at the inferior quadrant and decrease in VD of the ONH temporal quadrant in deep capillary plexus could be beneficial for diagnosing glaucoma in high myopia.

Abstract Glaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary open-angle glaucoma (POAG) in patients of European, African, Hispanic, and Eastern Asian descent. However, a significant gap in the literature exists regarding the prevalence of POAG in Middle Eastern (ME) populations. Current studies estimate ME POAG prevalence based on a European model. Herein we screened 65 total publications on ME prevalence of POAG and specific risk factors using keywords: “glaucoma”, “prevalence”, “incidence”, “risk factor”, “Middle East”, “Mideast”, “Persian”, “Far East”, as well as searching by individual ME countries through PubMed, Embase, Ovid, Scopus, and Trip searches with additional reference list searches from relevant articles published up to and including March 1, 2021. Fifty qualifying records were included after 15 studies identified with low statistical power, confounding co-morbid ophthalmic diseases, and funding bias were excluded. Studies of ME glaucoma risk factors that identify chromosomes, familial trend, age/gender, socioeconomic status, lifestyle, intraocular pressure, vascular influences, optic disc hemorrhage, cup-to-disc ratio, blood pressure, obstructive sleep apnea, and diabetes mellitus were included in this systematic review. We conclude that the prevalence of POAG in the ME is likely higher than the prevalence rate that European models suggest, with ME specific risk factors likely playing a role. However, these findings are severely limited by the paucity of population-level data in the ME. Well-designed, longitudinal population-based studies with rigorous inclusion and exclusion criteria are ultimately needed to accurately assess the epidemiology and specific mechanistic risk factors of glaucoma in ME populations.

Abstract The purpose of this study was to evaluate intraocular pressure (IOP) pre- and postoperatively, together with anterior chamber angle (ACA) parameters and biometrical results in cataract patients with or without open angle glaucoma (OAG). The prospective observational case–control study included 15 eyes with cataract and OAG in the glaucoma group and 25 eyes with only cataract in control group. Examination included full ophthalmic evaluation, IOP, ocular biometry and anterior segment optical coherence tomography measuring ACA pre- and 6 months postoperatively. OAG patients had a larger absolute IOP reduction compared to control group. Anterior chamber depth (ACD) and ACA width significantly increased in both groups. The OAG group had a tendency of narrower ACA preoperatively, but overall ACA parameters did not differ in either group pre- and postoperatively. The ACD change after surgery correlated with ACA parameters in the control group, but not in OAG group. Axial length was shorter postoperatively in the control group, but remained similar in the OAG group. Absolute IOP reduction was more pronounced in cataract patients with OAG than in cataract patients without glaucoma. ACD and ACA postoperatively increased in both groups and AL shortening was observed in non-OAG in cataract group.

Abstract Background Anterior chamber angle anatomy in perspective of ocular biometry may be the key element to intraocular pressure (IOP) reduction, especially in glaucoma patients. We aim to investigate anterior chamber angle and biometrical data prior to cataract surgery in patients with and without glaucoma comorbidity. Materials and methods This prospective comparative case-control study included 62 subjects (38 with cataract only and 24 with cataract and glaucoma). A full ophthalmic examination including, Goldmann applanation tonometry, anterior chamber swept source optical coherence tomography (DRI OCT Triton plus (Ver.10.13)) and swept source optical biometry (IOL Master 700 v1.7) was performed on all participants. Results We found that ocular biometry parameters and anterior chamber parameters were not significantly different among groups. However, when we added cut-off values for narrow angles, we found that glaucoma group tended to have more narrow angles than control group. IOP was higher in glaucoma group despite all glaucoma patients having medically controlled IOP. In all subjects, anterior chamber parameters correlated well with lens position (LP), but less with relative lens position, while LP cut-off value of 5.1 mm could be used for predicting narrow anterior chamber angle parameters. Conclusions Cataract patients tend to develop narrow anterior chamber angles. Anterior chamber angle parameters have a positive moderate to strong relationship with lens position. LP may be used predicting narrow angles.

Idiopathic intracranial hypertension (IIH) is characterized by isolated rise in intracranial pressure (ICP) leading to chronic, debilitating headaches, tinnitus, and vision loss. Conventional diagnostics and monitoring primarily require the use of invasive procedure like lumbar puncture to measure ICP, while traditional management strategies involve weight reduction and medical treatment with acetazolamide. In an effort to reduce the need for invasive procedures, noninvasive methods of ICP monitoring such as optic nerve sheath diameter measurements and two-depth transcranial Doppler ultrasonography have been developed. In cases of refractory and fulminant IIH, surgical management strategies such as optic nerve sheath fenestration (ONSF), ventriculoperitoneal (VP) and lumboperitoneal (LP) shunting, and transverse venous sinus stenting are used to relieve symptoms via ICP reduction. While ONSF and VP/LP shunting exhibit utility primarily for the treatment of vision loss and headache, respectively, venous sinus stenting may prove to be an effective option in the management of all symptoms of IIH. Most importantly, consideration of the patient’s individual symptoms and values should be taken into account when choosing the optimal surgical management strategy for patients with IIH.

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with “successfully” regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP’s relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.

Background: The purpose of this study was to examine the changes in IOP, total macular and RNFL, ganglion cell layer (GCL) thickness, and aqueous humour flare in open angle glaucoma (OAG) patients before and 6 months after cataract surgery. Methods: This was a prospective observational case–control age- and gender-matched study. Groups: 40 subjects in a controlled OAG (OAGc) group, 20 subjects in an uncontrolled OAG (OAGu) group, and 60 control group subjects. Examination: complete ophthalmic evaluation, IOP measurement, anterior and posterior segment Optical Coherence Tomography (OCT), and laser flare photometry before and 6 months postoperatively. Results: Six months postoperatively IOP decreased in all groups. An increase in macular thickness was found postoperatively in all groups. Preoperative aqueous humour flare was higher in the OAGc group than in the control group. After cataract surgery, aqueous humour flare was higher in the control group compared to the preoperative result. Conclusions: Changes in IOP following cataract surgery were strongly negatively correlated with preoperative IOP. An increase in macular thickness was observed 6 months postoperatively in all groups. Aqueous humour flare did not differ in OAGc and OAGu groups pre- and postoperatively but significantly increased in the control group postoperatively.

Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians.

This study investigated the agreement of intraocular pressure measurements using rebound tonometry and applanation tonometry in response to atmospheric changes in a hyperbaric chamber. Twelve eyes of 12 healthy subjects were included in this prospective, comparative, single-masked study. Intraocular pressure measurements were performed by rebound tonometry followed by applanation tonometry in a multiplace hyperbaric chamber at 1 Bar, followed by 2, 3 and 4 Bar during compression and again at 3 and 2 Bar during decompression. Mean differences between rebound and applanation intraocular pressure measurements were 1.6, 1.7, and 2.1 mmHg at 2, 3, and 4 Bar respectively during compression and 2.6 and 2.2 mmHg at 3 and 2 Bar during decompression. Lower limits of agreement ranged from -3.7 to -5.9 mmHg and upper limits ranged from -0.3 to 1.9 mmHg. Multivariate analysis showed that the differences between rebound and applanation intraocular pressure measurements were independent of atmospheric pressure changes (p = 0.79). Intraocular pressure measured by rebound tonometry shows a systematic difference compared to intraocular measured by applanation tonometry, but this difference is not influenced by changes of atmospheric pressure up to 4 Bar in a hyperbaric chamber. Agreement in magnitude of change between devices suggests rebound tonometry is viable for assessing intraocular pressure during atmospheric changes. Future studies should be designed in consideration of expected differences in IOP values provided by the two devices.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

Neurodegenerative disorders (NDD) such as Alzheimer's and Parkinson's diseases are significant causes of morbidity and mortality worldwide. The pathophysiology of NDD is still debated, and there is an urgent need to understand the mechanisms behind the onset and progression of these heterogenous diseases. The eye represents a unique window to the brain that can be easily assessed via non-invasive ocular imaging. As such, ocular measurements have been recently considered as potential sources of biomarkers for the early detection and management of NDD. However, the current use of ocular biomarkers in the clinical management of NDD patients is particularly challenging. Specifically, many ocular biomarkers are influenced by local and systemic factors that exhibit significant variation among individuals. In addition, there is a lack of methodology available for interpreting the outcomes of ocular examinations in NDD. Recently, mathematical modeling has emerged as an important tool capable of shedding light on the pathophysiology of multifactorial diseases and enhancing analysis and interpretation of clinical results. In this article, we review and discuss the clinical evidence of the relationship between NDD in the brain and in the eye and explore the potential use of mathematical modeling to facilitate NDD diagnosis and management based upon ocular biomarkers.

AimsTo examine the relationship between baseline structural characteristics of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) and functional disease progression in patients with open-angle glaucoma (OAG) over 5 years.Methods112 OAG patients were prospectively examined at baseline and every 6 months over a period of five years. Structural glaucomatous changes were examined with optical coherence tomography (OCT) and Heidelberg retinal tomography-III (HRT-III), and functional disease progression with automated perimetry (Humphrey visual fields). Cox proportional hazard models were used to assess the relationship between baseline structural measurements and functional disease progression.ResultsFrom baseline over a 5-year period, statistically significant increases were found in OCT disc (D) area (pConclusionBaseline ONH and RNFL structural characteristics were associated with a significantly shorter time to functional glaucomatous progression and visual field loss through the five-year period in OAG patients.

Purpose To compare macular choroidal thickness of idiopathic epiretinal membrane (ERM) and fellow eyes, and before and after vitrectomy in terms of the morphological features on spectral-domain optical coherent tomography (SD-OCT). Methods Eighty-four patients with unilateral idiopathic ERM were involved. Patients were categorized into: Group 1, ERM without membrane contraction; Group 2, ERM with membrane contraction and retinal folding; and Group 3, ERM with membrane contraction and macular edema. Twenty-two patients received surgical removal of ERM. Choroidal thickness was compared between ERM and fellow eyes, and before and after treatment. Results Mean choroidal thickness was significantly greater in ERM eyes than in fellow eyes (234.4 ± 22.5 vs 220.6 ± 20.8 μm; P

Optic-disc photography (ODP) has proven to be very useful for optic nerve evaluation in glaucoma. In real clinical practice, however, limited patient cooperation, small pupils, or media opacities can limit the performance of ODP. The purpose of this study was to propose a deep-learning approach for increased resolution and improved legibility of ODP by contrast, color, and brightness compensation. Each high-resolution original ODP was transformed into two counterparts: (1) down-scaled ‘low-resolution ODPs’, and (2) ‘compensated high-resolution ODPs’ produced via enhancement of the visibility of the optic disc margin and surrounding retinal vessels using a customized image post-processing algorithm. Then, the differences between these two counterparts were directly learned through a super-resolution generative adversarial network (SR-GAN). Finally, by inputting the high-resolution ODPs into SR-GAN, 4-times-up-scaled and overall-color-and-brightness-transformed ‘enhanced ODPs’ could be obtained. General ophthalmologists were instructed (1) to assess each ODP’s image quality, and (2) to note any abnormal findings, at 1-month intervals. The image quality score for the enhanced ODPs was significantly higher than that for the original ODP, and the overall optic disc hemorrhage (DH)-detection accuracy was significantly higher with the enhanced ODPs. We expect that this novel deep-learning approach will be applied to various types of ophthalmic images.

Impaired blood flow and oxygenation contribute to many ocular pathologies, including glaucoma. Here, a mathematical model is presented that combines an image-based heterogeneous representation of retinal arterioles with a compartmental description of capillaries and venules. The arteriolar model of the human retina is extrapolated from a previous mouse model based on confocal microscopy images. Every terminal arteriole is connected in series to compartments for capillaries and venules, yielding a hybrid model for predicting blood flow and oxygenation throughout the retinal microcirculation. A metabolic wall signal is calculated in each vessel according to blood and tissue oxygen levels. As expected, a higher average metabolic signal is generated in pathways with a lower average oxygen level. The model also predicts a wide range of metabolic signals dependent on oxygen levels and specific network location. For example, for high oxygen demand, a threefold range in metabolic signal is predicted despite nearly identical PO2 levels. This whole-network approach, including a spatially nonuniform structure, is needed to describe the metabolic status of the retina. This model provides the geometric and hemodynamic framework necessary to predict ocular blood flow regulation and will ultimately facilitate early detection and treatment of ischemic and metabolic disorders of the eye.

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight.

Purpose. To investigate potential associations between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in patients with primary open-angle glaucoma (POAG) and healthy subjects. Methods. Forty-three subjects were recruited. Weight and height were measured to calculate body mass index (BMI), along with blood pressure, heart rate, visual acuity, and IOP. Biometrics exam, corneal pachymetry, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular thickness were assessed. The visual field exam was performed on all patients, and both pattern standard deviation (PSD) and mean deviation (MD) were considered. CSFP was estimated indirectly by using the mathematical formula CSFP = 0.44 × BMI + 0.16 × diastolic pressure − 0.18 × age − 1.91, based on the previous scientific studies. The TLCPD was calculated as follows: IOP−CSFP. Results. A significant (p

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords “hydrocephalus glaucoma” and “normal-tension glaucoma shunt”. One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt-treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients.

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible.

The aim of this study was to compare the effects of nebulized mist and liquid drop applications on retrobulbar blood flow. A prospective, non-randomized clinical trial was used to collect data from 40 healthy human eyes. Color Doppler Imaging determined peak systolic (PSV) and end diastolic (EDV) blood flow velocities and resistance index (RI) in the ophthalmic artery after both applications. Measurements were taken at baseline and at 1 min post-treatment in both eyes with 5 min measurements in the treatment eye only. p values ≤ 0.05 were considered statistically significant. Mist application to treatment eye produced an increase in 1 min and 5 min PSV and EDV (0.001 < p < 0.03) and a decrease in 5 min RI (p = 0.01), with no significant changes in PSV, EDV or RI of control eye or in treatment eye 1 min RI (p > 0.05). Drop application to treatment eye produced an increase in PSV (p < 0.001) and EDV (p = 0.01) at 1 min, with an increase in control eye 1 min PSV and EDV (p = 0.03). There were no statistically significant changes in treatment eye PSV, EDV and RI after 5 min (p > 0.05). The use of nebulized mist may provide an effective alternative to liquid drop medication application.

Objective: To compare the effects of dorzolamide and timolol add-on therapy in open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. Methods: 35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated in a 3 month randomized, cross-over, single-masked study. During the experiments BP, heart rate, IOP and OPP were assessed 4 times per day (8–12–16–20 h). RBF was measured twice per day (8–20 h) using Color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed and vascular resistance (RI) calculated. Results: Both add-on therapies lowered IOP in a statistically significant manner from 15.7 ± 2.4 mmHg at latanoprost baseline to 14.9 ± 2.2 mmHg using dorzolamide (p < 0.001) and 14.2 ± 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was statistically significant at 20 h, favoring timolol as compared to dorzolamide (1.4 ± 2.4 vs. 0.2 ± 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed smaller IOP (2.0 ± 1.4), SPP (13.3 ± 7.9), systolic BP (13.5 ± 8.7) and diastolic BP (8.4 ± 5.4) fluctuations as compared to both latanoprost baseline or timolol add-on therapies. Higher difference between morning and evening BP was correlated to decreased evening CRA EDV in the timolol group (c = −0.41; p = 0.01). With increased MAP in the morning or evening hours, we found increased evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002 accordingly). Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased CRA EDV (c = −0.408; p = 0.01), increased CRA RI (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group. OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the timolol group. OPP fluctuations were not related to IOP fluctuations in both add-on therapies (p < 0.05). Conclusions: Both dorzolamide and timolol add-on therapies lowered IOP in a statistically significant fashion dorzolamide add-on therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of daytime OPP led to impaired RBF parameters in the evening.

Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI) and sub-Tenon’s infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME.

Adam M Moss, Alon Harris, Brent Siesky, Deepam Rusia, Kathleen M Williamson, Yochai ShoshaniDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USAAbstract: Topical hypotensive therapy with both timolol and carbonic anhydrase inhibitors has been shown to be efficacious at reducing intraocular pressure. Many prospective studies have also suggested that carbonic anhydrase inhibitors augment ocular blood flow and vascular regulation independent of their hypotensive effects. Although consistent in their findings, these studies must be cautiously interpreted due to the limitations of study design and specific blood flow imaging modalities. The purpose of this review is to appraise and critically evaluate the current body of literature investigating the effects of combined treatment with topical carbonic anhydrase inhibitors and timolol in patients with glaucoma with respect to ocular blood flow, visual function, and optic nerve head structure.Keywords: ocular blood flow, carbonic anhydrase inhibitor, timolol, glaucoma, visual function, optic nerve head

Rita Ehrlich1, Alon Harris1, Nisha S Kheradiya1, Diana M Winston1, Thomas A Ciulla3, Barbara Wirostko21Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, IN, USA; 2Stony Brook University Medical Center Research Way, Department of Ophthalmology, Stony Brook, NY, USA; 3Retina Service, Midwest Eye Institute, Attending Physician and Surgeon, Methodist Hospital, Indianapolis, IN, USAAbstract: Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.Keywords: age-related macular degeneration, aging, blood flow, eye, retina, macula, vision

Danny Moore, Alon Harris, Darrell WuDunn, Nisha Kheradiya, Brent Siesky1Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Primary open angle glaucoma (OAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and associated visual field loss. OAG is an emerging disease with increasing costs and negative outcomes, yet its fundamental pathophysiology remains largely undetermined. A major treatable risk factor for glaucoma is elevated intraocular pressure (IOP). Despite the medical lowering of IOP, however, some glaucoma patients continue to experience disease progression and subsequent irreversible vision loss. The scientific community continues to accrue evidence suggesting that alterations in ocular blood flow play a prominent role in OAG disease processes. This article develops the thesis that dysfunctional regulation of ocular blood flow may contribute to glaucomatous optic neuropathy. Evidence suggests that impaired vascular autoregulation renders the optic nerve head susceptible to decreases in ocular perfusion pressure, increases in IOP, and/or increased local metabolic demands. Ischemic damage, which likely contributes to further impairment in autoregulation, results in changes to the optic nerve head consistent with glaucoma. Included in this review are discussions of conditions thought to contribute to vascular regulatory dysfunction in OAG, including atherosclerosis, vasospasm, and endothelial dysfunction.Keywords: glaucoma, autoregulation, blood flow, atherosclerosis, vasospasm, endothelial dysfunction

Purpose. To assess differences in translaminar pressure gradient (TPG) and neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG, and healthy controls were included in the prospective pilot study (each group consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure (ICP), and confocal laser scanning tomography were assessed. TPG was calculated as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth transcranial Doppler device. The level of significance P < 0.05 was considered significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg), NRA (0.97(0.36) mm2), comparing with HTG and healthy subjects, P < 0.05. ICP was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy subjects (10.5(3.0) mmHg); however, the difference between groups was not statistically significant (P>0.05). The difference between TPG for healthy (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was statistically significant (P < 0.001). Higher TPG was correlated with decreased NRA (r = −0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure gradient was higher in glaucoma patients. Reduction of NRA was related to higher TPG in NTG patients. Further prospective studies are warranted to investigate the involvement of TPG in glaucoma management.

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved "b" wave amplitude (as measured by electroretinogram) within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration.

Purpose. To evaluate hemodynamic parameters as possible predictors for glaucoma progression. Methods. An 18-month randomized double-masked cohort study including 30 open-angle glaucoma patients receiving fixed-combination treatment with Dorzolamide/Timolol (DTFC) or Latanoprost/Timolol (LTFC) (n=15 per group) was performed. Intraocular pressure (IOP), arterial blood pressure (BP), ocular and diastolic perfusion pressures (OPP, DPP), color Doppler imaging, pulsatile ocular blood flow analysis, scanning laser polarimetry, and Humphrey visual field evaluations were included. Results. Both treatments showed statistically similar IOP reduction. Six patients in DTFC and 7 in LTFC group met glaucoma progression criteria. DTFC group had higher OPP, DPP, and lower vascular resistivity indices as compared to the LTFC. Progressing patients had higher nerve fiber index, lower systolic BP, OPP, DPP, higher ophthalmic and central retinal artery vascular resistance, and lower pulse volume (P