Search

Glaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary openangle 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.

Glaucoma is a multifactorial progressive and degenerative optic neuropathy representing one of the world's leading cause of irreversible blindness. Currently, reduction of intraocular pressure remains the only universally approved therapy, yet a wealth of studies has identified significant vascular contributions to the disease process in certain individuals. Population-based studies have identified important racial disparities and differential risk factors in glaucoma prevalence, incidence, and progression. A more significant vascular component has been identified in persons of African descent. Elucidating risk modifiers, including genetic and racial influence, is important when considering individually tailored clinical management of glaucoma. The application of artificial intelligence and mathematical modeling inclusive of demographic considerations, vascular health, and clinical biomarkers may help reduce disease disparities, advance personalized medicine, and provide a comprehensive model of glaucoma.

Purpose To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational relevance This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Purpose: To investigate the pre-operative conjunctival flora in patients undergoing cataract surgery with major local and/or systemic risk factors for developing post-operative infection. Methods: A total of 83 patients underwent bacterial culture and sensitivity testing of conjunctival swabs obtained from both eyes because of local risk factors at the pre-operative visit (i.e. chronic blepharitis, conjunctivitis, or lacrimal system disease), and/or systemic risk factors (i.e. autoimmune or skin disorders) for developing post-operative infection. If the swab was found positive, an antimicrobial susceptibility test was performed, and a specific antibiotic therapy was administered. Surgery was performed when a repeat conjunctival swab (after antibiotic treatment) showed negative cultures. Results: Cultures were found positive in 25.3% of patients. Staphylococcus aureus (18%) and Staphylococcus epidermidis (15%) were the most frequently isolated microorganisms. Gram-negative bacteria, including Pseudomonas aeruginosa, were present in nine cases (8%). Conclusion: Present results showed a low rate of swab positivity compared to previous published data, and slightly different microbial flora. The differences observed may be caused by geographical factors and/or to the specific characteristics of the subgroup of studied patients. Considering that the surface microbial flora is one of the major causes of endophthalmitis, this information may be useful in selecting antibacterial regimens to prevent serious ocular infections, and restrain the increasing problem of antibiotic resistance.

Systemic pathologies such as diabetes and hypertension affect different organs and systems in the body. However, the first signs of these pathologies often emerge as alterations in visual and structural functions in the eye. As a consequence, the ophthalmologist is often the first physician to make a diagnosis of systemic diseases. In fact, the eye represents a unique organ where signs of systemic diseases may be assessed with non-invasive techniques.

To evaluate diurnal variations in optic nerve head (ONH) vessel density assessed by optical coherence tomography angiography (OCT-A) in healthy subjects, ocular hypertension (OHT), and open-angle glaucoma (OAG) patients. Forty subjects (OAG, 21; OHT, 6; healthy, 13) were assessed for vessel density percentage (VD%) and flow index in the ONH (NH VD%, NH index), and in the radial peripapillary capillary layer (RPC VD%, RPC index) at 9:00, 11:00, 14:00, 16:00, and 18:00 on a single day. Repeated measures ANOVAs were used to test for changes in the parameters measured at multiple time points. All OCT-A parameters analyzed at the different time points were statistically lower in the OAG patients compared to both the OHT and healthy groups (p 0.05). In healthy subjects, OHT and OAG patients, the variations in the OCT-A derived parameters were relatively small. These results suggest that in the clinical practice the OCT-A assessment can be performed independently of the time of the day, contrasting IOP evaluation.

Glaucoma, the world’s leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.

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.

Purpose: To evaluate morphological differences in retinal nerve fibers layers (RNFL), optic nerve head (ONH), ganglion cell complex (GCC), and macular thickness between amblyopic and normal eyes from spectral domain optical coherence tomography (SD-OCT). Methods: Of 234 eyes of 117 children, four groups emerged: group A (162 eyes of 81 non-amblyopic subjects); group B (32 fellow eyes of 32 subjects with monolateral amblyopia); group C (32 amblyopic eyes of 32 subjects affected by monolateral amblyopia); group D (8 amblyopic eyes of 4 subjects with bilateral amblyopia). Patients underwent SD-OCT for ONH parameters, RNFL, GCC and macular thickness, retina map, and ONH scan quality index (SQI). Two-sided p values Results: Parameters with a significant difference between groups ( p 2 in group A and 1.76 (0.68) mm2 in group C; disk area, 2.43 (0.45) mm2 in group A and 2.02 (0.71) mm2 in group C; central macular thickness, 250.99 (19.74) µm in group A and 267.16 (23.52) µm in group C; nerve fiber ONH SQI, 62.82 (13.15) in group A, 51.26 (15.55) in group C, 48.29 (14.37) in group D; retina map SQI, 63.34 (10.34) in group A and 57.34 (9.84) in group C. For other parameters no significant difference was observed ( p > 0.005). Conclusions: Amblyopia may influence optic nerve morphology, central macular thickness, and OCT scan quality. RNFL and GCC are not affected by monolateral amblyopia.

Biomarkers of ocular blood flow originating from a wide variety of imaging modalities have been associated with glaucoma onset and progression for many decades. Advancements in imaging platforms including optical coherence tomography angiography (OCTA) have provided the ability to quantify vascular changes in glaucoma patients, alongside traditional measures such as retinal nerve fiber layer thickness (RNFL) and optic nerve head (ONH) structure. Current literature on vascular biomarkers, as measured by OCTA, indicates significant relationships between glaucoma and blood flow and capillary density in the retina and ONH. The data currently available, however, is highly diverse and lacks robust longitudinal data on OCTA vascular outcomes and glaucoma progression. Herein we discuss and summarize the relevant current literature on OCTA vascular biomarkers and glaucoma reviewed from December 14, 2020 through March 1, 2021. Associations between OCTA vascular biomarkers and clinical structural and functional glaucoma outcomes as well as differences between glaucoma patients and healthy controls are reviewed and summarized. The available data identifies significantly decreased flow density, flow index, and vessel density in the ONH, peripapillary vascular layer, and macula of glaucoma patients compared to controls. Whole image vessel density is also significantly decreased in glaucoma patients compared to controls and this outcome has been found to correspond to severity of visual field loss. OCTA vascular biomarkers alongside clinical structural outcomes may aid in assessing overall risk for glaucoma in patients.

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.

Purpose The current understanding of circadian regulation disorders and their involvement in glaucoma pathophysiology are poorly understood, yet they may have a substantial impact on the onset and progression of glaucoma. Herein, we review and summarize all the available literature on circadian rhythm disorder and glaucoma to uncover the impact on glaucoma risk, and we highlight future research and potential novel targets for glaucoma management. Materials and methods A review of the relevant literature was performed through PubMed through August 1, 2019. Results Within a normal circadian rhythm, intraocular pressure (IOP) peaks at night, whereas blood pressure (BP) troughs at night. High nocturnal IOP coupled with low nocturnal systemic BP results in low ocular perfusion pressure and potential for unobserved damage to retinal tissues and the optic nerve. Circadian-related melatonin and sleep disorders also result in changes in IOP and ocular perfusion pressure that lead to the progression of glaucoma. In addition, impaired perception of light input due to glaucoma can subsequently lead to abnormal serum levels of melatonin, resulting in circadian rhythm misalignment. This disruption of the circadian rhythm also contributes to sleep and mood disorders, common in individuals with glaucoma. As regards treatment, glaucoma medications that lower nocturnal IOP without influencing nocturnal BP or diminishing circadian variation seem most effective. Conclusions Glaucoma progression is influenced by multiple physiological factors regulated by the circadian rhythm. Progression of the disease may also cause physiological changes that lead to circadian-related issues. Further research is warranted on the diurnal cycle, melatonin-mediated processes, and their influence on glaucoma management.

Précis: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. Purpose: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. Methods: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch’s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. Results: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P

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.

Carbonic anhydrase inhibitors (CAIs) have been used for many decades in the treatment of glaucoma. Systemic CAIs were an early treatment option to lower intraocular pressure by reducing aqueous humour production; however, frequent side effects including polyuria and paresthesia contributed to the eventual development of topical CAIs. As topical drug development evolved over time, prostaglandin analogues and beta-blockers have become the gold standard of glaucoma therapies. Although prescribed less often than other classes of topical glaucoma therapies, topical CAIs continue to be used in combination therapies with beta-blockers and alpha agonists. Topical CAIs have also been demonstrated to alter biomarkers of ocular haemodynamics, which have relevance in glaucoma. The purpose of this review is to review and summarise the current state of topical CAI prescribing trends, known efficacy and suggested mechanisms and potential influence on ocular haemodynamics for the future of glaucoma management.

We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption. The vitreous and the choroid are located at the macula boundary and provide oxygen via boundary conditions of Dirichlet type. The three capillary plexi (superficial, intermediate, and deep) of the retinal circulation pierce the macular layers and provide oxygen via a volumetric source that depends on the retinal blood flow. Oxygen profiles through the macular tissue are calculated by simulating the balance among oxygen supply, consumption and diffusion in: (a) physiological baseline conditions; (b) retinal blood flow reduced by 10%, 30% and 50% with respect to baseline; (c) choroidal oxygen level diminished by 10%, 30% and 50% with respect to baseline. Model simulations predict that: (1) the oxygenation of the foveal avascular zone is not affected by reduction in retinal blood flow; (2) a reduction in choroidal oxygen supply significantly affects the outer layers, especially the photoreceptors and outer nuclear layers; (3) the impact of reduction in choroidal oxygen supply is larger in the region more proximal to the macular center; (4) the impact of reduction in retinal blood flow is larger in the region more proximal to the macular periphery. The proposed mathematical model suggests that changes in retinal and choroidal oxygen supplies impact the oxygenation of the macular tissue differentially. These results may help better understand the pathogenesis of macular degeneration.

Purpose: To examine the nature and frequency of ocular side effects due to systemic target therapy with BRAF and MEK inhibitors as well as immunotherapy with cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) monoclonal antibodies used in the treatment of cutaneous malignant melanoma (CMM). Design: While proven effective in cancer treatment, target therapy and immunotherapy have been associated with ocular side effects likely due to their ability to alter the immune privilege of the eye. We conducted a retrospective chart review of patients undergoing target and immunotherapy for CMM and documented all associated eye findings. Methods: We reviewed the records of 34 patients receiving target and immunotherapy for CMM who were examined in the academic ophthalmology clinic between 2012 and 2017. Results: Ocular side effects were present in 41.1% of patients in this study with 14.7% presenting with uveitis. Patients undergoing therapy with either vemurafenib only or dabrafenib/trametinib combination therapies comprised 70.5% of the study cohort. Ocular side effects occurred in 45.5% and 46.1% of patients on vemurafenib and dabrafenib/trametinib combination therapy, respectively. About 47.5% of males presented with ocular side effects compared to 30.5% of females. Notably, 13/14 patients with ocular symptoms recovered. Conclusion: This study highlights the frequency of ocular side effects in patients treated with target therapy and immunotherapy for CMM and shows that symptom resolution can be effectively achieved with proper ophthalmic care. Further research is required to answer whether cessation of these therapies is mandatory during ophthalmic treatment.

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. Since 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 (ii) 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 occuring at the scale of the whole eye, for which clinical assessment is feasible.

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 examine the relationship between the cardiovascular status and variations in optical coherence tomography (OCT)-derived parameters of the peripapillary and macular tissues, and macular vascular flow area measured by optical coherence tomography angiography (OCTA) in healthy subjects. Design: Prospective, open-label, non-randomized clinical study. Methods: Twenty one eyes of 21 healthy subjects were analyzed using a swept-source device, including OCT and OCTA acquisitions. Cardiovascular changes were investigated by performing a practical hand-grip test (HGT). Blood pressure, heart rate, OCT and OCTA structural and vascular changes were measured and analyzed before and after the HGT-induced exercise. Results: The mean patient age was 34.0 (± 15.2) years. While both diastolic and systolic blood pressures increased significantly aft er exercise (p < 0.001 and p = 0.003, respectively), the heart rate did not show a significant increment (p = 0.182). OCT structural parameters of the optic nerve did not change significantly. Instead, a significant redistribution of choroidal thickness (CT) was observed in the macular region, with a significant reduction (-6.5%, p = 0.001) in the outer-nasal macular sector after exercise. OCTA acquisitions did not show changes in the vascular density of both the superficial retinal layer and deep retinal layer. Conclusions: We demonstrated that HGT-induced exercise can moderately elevate blood pressure without detectable effects on OCTA-derived parameters in healthy young subjects. Moreover, it produced a significant redistribution of CT. Further studies are needed to better explain the possible role of HGT in the characterization of the pathophysiology of ocular diseases associated with abnormalities of the vascular function such as glaucoma, age-related macular degeneration, and diabetic retinopathy.

PURPOSE. To compare the diagnostic capability of three-dimensional (3D) macular parameters against traditional two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography. To determine if manual correction and interpolation of B-scans improve the ability of 3D macular parameters to diagnose glaucoma. METHODS. A total of 101 open angle glaucoma patients (29 with early glaucoma) and 57 healthy subjects had peripapillary 2D RNFL thickness and 3D macular volume scans. Four parameters were calculated for six different-sized annuli: total macular thickness (M-thickness), total macular volume (M-volume), ganglion cell complex (GCC) thickness, and GCC volume of the innermost 3 macular layers (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer). All macular parameters were calculated with and without correction and interpolation of frames with artifacts. The areas under the receiver operating characteristic curves (AUROC) were calculated for all the parameters. RESULTS. The 3D macular parameter with the best diagnostic performance was GCC-volume-34, with an inner diameter of 3 mm and an outer of 4 mm. The AUROC for RNFL thickness and GCC-volume-34 were statistically similar for all regions (global: RNFL thickness 0.956, GCC-volume-34 0.939, P value = 0.3827), except for the temporal GCC-volume-34, which was significantly better than temporal RNFL thickness (P value = 0.0067). Correction of artifacts did not significantly change the AUROC of macular parameters (P values between 0.8452 and 1.0000). CONCLUSIONS. The diagnostic performance of best macular parameters (GCC-volume-34 and GCC-thickness-34) were similar to or better than 2D RNFL thickness. Manual correction of artifacts with data interpolation is unnecessary in the clinical setting.

Glaucoma is one of the world’s leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to be the result of elevated intraocular pressure (IOP), leading to optic nerve damage and functional vision loss. Recently, researchers have suggested that POAG may have an underlying genetic component. In fact, studies of genetic association and heritability have yielded encouraging results showing that glaucoma may be influenced by genetic factors, and estimates for the heritability of POAG and disease-related endophenotypes show encouraging results. However, the vast majority of the underlying genetic variants and their molecular mechanisms have not been elucidated. Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (LMX1B, MADD, NR1H3, and SEPT9), and VCDR (ABCA1, ELN, ASAP1, and ATOH7). Still, genetic studies about glaucoma and its molecular mechanisms are limited by the multifactorial nature of the disease and the large number of genes that have been identified to have an association with glaucoma. Therefore, further study into the molecular mechanisms of the disease itself are required for the future development of therapies targeted at genes leading to POAG endophenotypes and, therefore, increased risk of disease.

Purpose The aim of this paper is to concisely summarize what is currently known about OAG among persons of LAD in the United States for the purpose of improving individualized care and highlighting areas requiring further study. Materials and methods Review of relevant literature was performed through PubMed and Google Scholar from October 1978 through November 11, 2019. Results As the Latin American population grows within the United States, it is predicted that by 2050, men of LAD will make up the largest demographic group with OAG. Persons of LAD experience a greater increase in OAG prevalence per decade of life compared with persons of African descent and may have unique risk factors. In particular, those with African ancestry and hypertension are at greater risk of elevated intraocular pressure (IOP). Maximum IOP, variability in IOP, and diabetes are also important considerations. Unique anatomic and physiological characteristics such as scleral tensile strain, longer axial length, thin corneas, and corneal hysteresis may play a role in this population's unique risk for the development and progression of OAG. Conclusions OAG represents a growing concern among persons of LAD in the United States; however, information on specific risk factors in this population currently remains limited. Studies should be designed to investigate the LAD population and their respective structural, vascular, and social risk factors for the development and progression of OAG to assist clinicians in improving outcomes for this growing population.

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<0.05) difference was found between the two groups for several parameters. Specifically, the CSFP was lower in patients with POAG than in healthy subjects (8.14 ± 4.52 and 7.43 ± 2.06, p<0.001, respectively). Anamnestic TLCPD was found to be significantly (p<0.001) higher in patients with POAG compared to healthy subjects. A significant (p<0.05) correlation was found between anamnestic TLCPD and MD (r = −0.31), inferior RNFL thickness (r = −0.29), superior RNFL thickness (r = −0.27), IOP (r = 0.22), and CSFP (r = −0.46). Conclusion. The CSFP was lower in glaucomatous patients compared to healthy subjects, whereas the TLCPD was higher in glaucomatous patients compared to healthy subjects, even though this difference was not statistically significant. A higher TLCPD may damage the RNFL, resulting in functional visual field impairment.

Background and Hypothesis: Reduction of intraocular pressure (IOP) resulting from overproduction or impaired outflow of aqueous humor is, to date, the only approved medical treatment for the disease. IOP is determined by the balance between aqueous humor production at the ciliary body and drainage at the anterior chamber angle. A mathematical model describing aqueous humor (AH) flow was employed in order to study the effects of glaucoma medications and risk factors on IOP. Experimental Design or Project Methods: IOP can be calculated as the unknown variable in the mathematical balance between AH inflow (Jin) and outflow (Jout). Model simulations using MATLAB were used to calculate IOP in conditions of varied trabecular meshwork resistance (R) over changes in episcleral venous pressure (EVP), uveosclearal outflow facility (Cuv), and ciliary capillary blood pressure (cBP) in order to simulate the effects of EVP reducing medications, prostaglandin analogs, and systemic BP, respectively. Results: The simulated effects of EVP reducing medications and prostaglandin analogs led to IOP decrease of 13.12%, 5.51%, and 2.88% for conditions of R0, 3R0, and 6R0, respectively, where R0 is equal to the trabecular meshwork resistance when IOP = EVP. The simulated effects of prostaglandin analogs resulted an IOP decrease of 13.73%, 18.34%, and 19.83%, for conditions of R0, 3R0, and 6R0, respectively. The simulated effects of increasing systemic BP resulted in an IOP increase of 49.88%, 58.51%, and 60.71% for conditions of R0, 3R0, and 6R0, respectively. Conclusion and Potential Impact: The model simulations predict differential efficacy in IOP reducing medications in patients of varied R as well as the differential impact of systemic BP on IOP in patients of varied R. This model has the potential to predict the IOP reducing effect of medications in an individual as well as the impact of risk factors such as systemic BP on IOP.

Background and Hypothesis: Age-related macular degeneration (AMD) is the leading cause of adult blindness in the developed world, and can be classified as one of two types: dry or wet. Abnormalities in retinal and choroidal vasculature may influence dry-to-wet conversion. This study represents a first attempt to use mathematical modeling to characterize the impact of retinal and choroidal blood flow on the oxygenation of retinal layers at various distances from the macula, in healthy individuals and AMD patients. Experimental Design or Project Methods: The macula is modeled as 7 layers: ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptors layer (PH), retinal pigmented epithelium (RPE). Oxygen supply is provided by the vitreous, the choroid, and by three retinal capillary plexi. Oxygen profiles through the macular tissue are calculated by simulating the balance between O2 supply, consumption and diffusion in: physiological baseline conditions; AMD conditions. Results: Choroidal vasculature impairment affects tissue more proximal to the macular center, retinal blood flow impairment affects tissue more proximal to the macular periphery, and oxygenation of the foveal avascular zone is not affected by retinal vasculature impairment. The decrease in oxygenation due to retinal and choroidal blood flow impairment in AMD is more prominent in the RPE, PH and ONL in all three anatomical zones of the macula. Conclusion and Potential Impact: Our mathematical model revealed that reduced choroidal and retinal oxygenation in AMD patients mostly affects the RPE and PH layers, regardless of the distance from the macula. This finding may explain hypoxia inducible factor-1 (HIF-1) production in these layers, which leads to enhanced vascular endothelial growth factor (VEGF) production, causing neovascularization and conversion to wet AMD. Our model suggests that treatment modalities aimed at maintaining stable oxygenation in dry AMD patients may prevent conversion to wet AMD, and reduce vision loss in these patients.

Traumatic brain injury is represented by a penetrating or non-penetrating head injury, which causes disruption in the normal functioning of the brain. Traumatic brain injury has been an ardently debated topic of discussion due to its prevalence in media centric persons such as military personnel and athletes. Current assessments for traumatic brain injury have looked at vestibulo-ocular and vascular parameters to aid in diagnosis. Innovations in non-invasive ophthalmic imaging have allowed for the visualization of specific tissue structure/function relationships in a variety of ophthalmic and neurodegenerative diseases. As the eye and brain share significant embryological and physiological pathways, ocular imaging modalities may provide a novel and impactful tool in advancing assessment of traumatic brain injury. Herein, we examined the available literature and data on visual fields, mean retinal nerve fiber layer thickness, retinal ganglion cell layer thickness, and cerebral blood flow following traumatic brain injury. This review of published individual and population-based studies was performed in order to explore the feasibility and importance of considering ocular imaging biomarkers following traumatic brain injury.

Assessment and monitoring of intracranial pressure (ICP) are important in the management of traumatic brain injury and other cerebral pathologies. In the eye, ICP elevation and depression both correlate with optic neuropathies, the former because of papilledema and the latter related to glaucoma. While the relationship between ICP elevation and papilledema is well established, the relationship between low ICP and glaucoma is still poorly understood. So far, ICP monitoring is performed invasively, but this entails risks including infection, spurring the study of non-invasive alternatives. We review 11 methods of non-invasive estimation of ICP including correlation to optic nerve sheath diameter, intraocular pressure, ophthalmodynamometry and two-depth transcranial Doppler of the ophthalmic artery. While none of these methods can fully replace invasive techniques, certain measures show great potential for specific applications. Although only used in small studies to date, a MRI based method known as MR-ICP, appears to be the best non-invasive technique for estimating ICP, with two-depth transcranial ultrasound and ophthalmodynamometry showing potential as well.

Studies have confirmed that optic disc haemorrhage (ODH) is a significant risk factor for the development and progression of primary open-angle glaucoma (POAG). Various populations have differing risk factors for developing POAG. As such, a literature review was conducted examining seven studies published in India, China, Japan, Australia, Korea and the USA. The goal of this review was to better identify ODH risk factors and their relationship to development and progression of POAG. Ultimately, patients with ODH have a greater risk for developing POAG across all populations analysed in this review. However, some populations demonstrated additional risk factors for ODH, such as increasing age and female gender. Paradoxically, data from several studies show that people of African descent have a reduced risk of ODH despite having increased risk of open-angle glaucoma than their Caucasian counterparts. By parsing out the complex relations between ODH and open-angle glaucoma stratified by age, gender and race, we may gain a broader understanding of glaucoma pathogenesis and derive individualised treatment strategies.

Introduction: To identify novel velocity waveform parameters of the ophthalmic artery and central retinal artery by computer-aided image processing of Doppler ultrasonography measurements, and to evaluate correlations between the waveform parameters and different demographics and disease severity of open-angle glaucoma patients. Methods: Thirty-six images of 36 open-angle glaucoma patients were considered. A semiautomated image processing code was used to detect the digitalized ophthalmic artery and central retinal artery velocity waveforms and to extract the waveform parameters. Concordance correlation coefficient, two-sample t-test, and Pearson’s correlation coefficient were used to test for similarities, differences, and associations among variables. Results: Female glaucoma patients showed a statistically higher ophthalmic artery normalized distance between ascending and descending limb (p = 0.004), hypertensive glaucoma patients a statistically higher ophthalmic artery peak systolic velocity time (p = 0.025), glaucoma patients with hyperlipidemia a statistically higher ophthalmic artery resistivity index (p = 0.023) and a statistically higher ophthalmic artery peak systolic velocity acceleration (p = 0.025), glaucoma patients with cardiovascular diseases a statistically lower central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.033) and a statistically higher central retinal artery period (p = 0.028), and patients with different body mass index a statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.016). Groups with different disease severity, classified following the Brusini glaucoma staging system 2, showed statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p Discussion: Ophthalmic artery and central retinal artery computer-aided analysis of velocity waveforms could identify novel waveform parameters capable of differentiating among different demographics and disease severity of open-angle glaucoma patients.

Abstract. Introduction: To investigate the effects of a lutein complex supplementation on ocular blood flow in healthy subjects. Materials and Methods: Sixteen healthy female patients (mean age 36.8 ± 12.1 years) were enrolled in this randomized, placebo-controlled, double-blinded, two-period crossover study. Subjects received daily an oral dose of the lutein with synergistic phytochemicals complex (lutein (10 mg), ascorbic acid (500 mg), tocopherols (364 mg), carnosic acid (2.5 mg), zeaxanthin (2 mg), copper (2 mg), with synergistic effects in reducing pro-inflammatory mediators and cytokines when administered together in combination) and placebo during administration periods. Measurements were taken before and after three-week supplementation periods, with crossover visits separated by a three-week washout period. Data analysis included blood pressure, heart rate, intraocular pressure, visual acuity, contrast sensitivity detection, ocular perfusion pressure, confocal scanning laser Doppler imaging of retinal capillary blood flow, and Doppler imaging of the retrobulbar blood vessels. Results: Lutein complex supplementation produced a statistically significant increase in mean superior retinal capillary blood flow, measured in arbitrary units (60, p = 0.0466) and a decrease in the percentage of avascular area in the superior (−0.029, p = 0.0491) and inferior (−0.023, p = 0.0477) retina, as well as reduced systolic (−4.06, p = 0.0295) and diastolic (−3.69, p = 0.0441) blood pressure measured in mmHg from baseline. Data comparison between the two supplement groups revealed a significant decrease in systemic diastolic blood pressure (change from pre- to post-treatment with lutein supplement (mean (SE)): −3.69 (1.68); change from pre- to post-treatment with placebo: 0.31 (2.57); p = 0.0357) and a significant increase in the peak systolic velocity (measured in cm/sec) in the central retinal artery (change from pre- to post-treatment with lutein supplement: 0.36 (0.19); change from pre- to post-treatment with placebo: −0.33 (0.21); p = 0.0384) with lutein complex supplement; data analyses from the placebo group were all non-significant. Discussion: In healthy participants, oral administration of a lutein phytochemicals complex for three weeks produced increased ocular blood flow biomarkers within retinal vascular beds and reduced diastolic blood pressure compared to placebo.

Advancements in imaging technologies over the past several decades have allowed for the identification of non-intraocular pressure (IOP) processes involved in glaucomatous optic neuropathy. Perhaps the most commonly cited non-IOP risk factors are impaired ocular circulation and/or faulty vascular regulation and vasospasm [1, 2]. Other important considerations include the possible synergistic interaction between IOP and intracranial pressure (ICP) and their effects on ocular structure and circulation [3]. The ability to assess ICP in glaucoma has been significantly limited by the highly invasive nature of ICP measurements. Recently, the ability to quantify ICP noninvasively has significantly improved, with pilot data suggesting a link between low ICP and glaucoma [4]. Even though the limited data on the topic prevents us from drawing definitive conclusions, the emergence of noninvasive assessment protocols holds great promise to define the pathway of ICP’s involvement in glaucoma. In this article, new data and analysis on cerebrospinal fluid pressure (CSFp) and its impact on optic nerve and retinal microcirculation will be explored alongside the broader implications of ICP in glaucoma. One difficulty in interpreting ICP as a risk factor for the onset and progression of glaucoma is the interplay and possible synergies among IOP, ICP, and the ocular circulation. Advances in physically based mathematical modeling have recently allowed for the exploration of glaucoma risk factor interconnectivity [5–9], providing further insight into glaucoma pathophysiology, and eventually may allow for individualized screening and improved patient-specific treatment options [10]. The concepts of ICP, pilot data, and future paradigms in glaucoma management are presented herein, with a focus on comprehensively understanding the role and impact that ICP may have on glaucomatous optic neuropathy.

This chapter provides an overview of the main structural and functional properties of the ocular vasculature. Four major circulatory systems within the eye are considered, namely those nourishing the retina, the optic nerve head, the choroid, and the anterior segment. Some aspects related to vascular regulation and innervation are also discussed, along with outstanding questions that remain a matter of debate.

Purpose: Arterial waveform parameters (WPs) are commonly used to monitor and diagnose systemic diseases. Color Doppler Imaging (CDI) is a consolidated technique to measure blood velocity profile in some of the major ocular vessels. This study proposes a computer-aided manipulation process of ophthalmic artery (OA) CDI images to classify and quantify WPs that might be significant in the assessment of glaucoma.Methods: Fifty CDI images acquired by four different operators on nine healthy individuals and 38 CDI images of 38 open-angle glaucoma (OAG) patients were considered. An ad-hoc semi-automated image processing code was implemented to detect the digitalized OA velocity waveform and to extract the WPs. Concordance correlation coefficient (CCC), two-sample t-test and Pearson’s correlation coefficient were used to test for similarities, differences and associations among variables.Results: The OA-CDI images manipulation proposed showed a higher concordance between measured peak systolic velocity (PSV) data and extracted PSV data (0.80≤CCC≤0.98) than on end diastolic velocity (EDV) (0.45≤CCC≤0.63) and resistive index (RI) (0.30≤CCC≤0.58) data. In OAG patients, EDV, RI, subendocardial viability ratio (SEVR), period (T), area ratio (f) and normalized distance between ascending and descending limb (DAD/T) were found statistically correlated to at least one of the following factors: gender, age, ocular medications and year of diagnosis. When compared to healthy individuals, OAG patients OA-CDI profiles showed statistically higher values of f (p < 0.001) and DAD/T (p = 0.002) (p-values corrected by age and gender).Conclusion: The proposed computer-aided manipulation of OA-CDI images allowed to identify DAD/T as a novel WP that vary significantly among healthy individuals and OAG patients, and among female and male OAG patients. Future studies on longitudinal OAG data are suggested to investigate the potential of DAD/T to predict severity and progression of the disease.

Purpose: The aim of this study was to examine ocular blood flow parameters that may predict structural and functional disease progression in open-angle glaucoma (OAG) patients of different diabetic status, gender, ethnicity, and body mass index (BMI).Methods: One hundred twelve patients with OAG were assessed for systemic blood pressure (BP), ocular perfusion pressure (OPP), retrobulbar blood flow, capillary blood flow, and optic nerve head morphology at baseline and every six months for a five-year period. Structural progression was monitored with optical coherence tomography and Heidelberg retinal tomography-III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Factors associated with OAG structural and functional progression were analyzed using Cox proportional hazards models.Results: The following were associated with shorter time to structural progression: In diabetic patients, larger area of avascular space; in males, lower central retinal artery peak systolic velocity and end diastolic velocity; in patients of African descent, higher systolic BP and OPP; in obese patients, lower ophthalmic artery end diastolic velocity. The following were associated with shorter time to functional progression: In diabetic patients, cup area, cup volume, cup/disc area ratio, linear cup/disc ratio, mean cup depth, cup shape; in males, systolic BP, diastolic BP, mean arterial pressure, systolic PP, diastolic PP, OPP, mean PP; in overweight patients, higher ophthalmic artery and central retinal artery resistive indices; in obese patients, lower central retinal artery resistive index.Conclusions: Structural and functional OAG disease progression may be influenced differently in patients based on diabetic status, gender, ethnicity, and BMI. Mathematical modeling of risk variables that takes into account demographic characteristics may assist in better identifying OAG progression risk.

PURPOSE To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years. MATERIALS AND METHODS In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to 4-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. RESULTS In OAG patients of AD, structural changes of the ONH demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over 4 years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of AD, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. CONCLUSIONS Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the ONH and macular thickness over 4 years in OAG patients of AD compared with ED. These data suggest that ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of AD compared with ED.

Primary open-angle glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell loss and subsequent visual field impairment. Elevated intraocular pressure remains the only treatable and modifiable risk factor and vascular impairment has been demonstrated in glaucomatous patients. New research has uncovered varying and often contradictory data suggesting more than just a casual correlation with ethnicity, diabetes, gender, obesity and age. Little is known about each variables’ contribution to the etiology of glaucoma and how their presence or absence with other risk factors potentiate or reduce an individual’s overall risk. The realization that glaucoma is more than a simple, binary disease necessitates a next-generation mathematical model with the capability to integrate individual patient characteristics and clinical risk factors to predict its formation and progression.

The aim of the Mont Blanc Study was to investigate the relationship between intraocular pressure (IOP), central corneal thickness (CCT), and altitude in healthy subjects. Thirty-three eyes of 33 healthy volunteers (mean age: 24.8 years, 17 females) had their IOP measured with Perkins and I-Care tonometers and their CCT using ultrasound pachymetry at three locations in Italy with different altitudes: Pavia, (PV), 77 meters above sea level (a.s.l); Courmayeur (CM), 1300 meters a.s.l; Pointe Helbronner (PH), 3466 meters a.s.l.). The measurements were performed at 9 am, 11 am, 1 pm and 3 pm (±30’) in indoor settings (mean temperature of 19°C) in PV and PH. At 9 am, CCT and IOP were measured outdoor (mean temperature of -1.4°C) at PH. The mean values of the IOP curve decreased from PV to PH with the Perkins (p = 0.02) and I-Care tonometers (p = 0.001). Instead, CCT increased upon ascension from PV to PH (p = 0.01), and from CM to PH (p = 0.002). When exposed to sub-zero temperature, the IOP increased (p

Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and visual field loss. Some speculate that sex plays a role in the risk of developing POAG and that the physiological differences between men and women may be attributed to the variable effects of sex hormones on intraocular pressure, ocular blood flow, and/or neuroprotection. Estrogen, in the form of premenopausal status, pregnancy, and postmenopausal hormone therapy is associated with an increase in ocular blood flow, decrease in intraocular pressure and neuroprotective properties. The vasodilation caused by estrogen and its effects on aqueous humor outflow may contribute. In contrast, although testosterone may have known effects in the cardiovascular and cerebrovascular systems, there is no consensus as to its effects in ocular health or POAG. With a better understanding of sex hormones in POAG, sex hormone-derived preventative and therapeutic considerations in disease management may provide for improved sex-specific patient care.

The relationship between ocular haemodynamics and retinitis pigmentosa (RP) has not been fully understood. Reductions in blood flow have been established in RP patients by a variety of studies; however, questions have yet to be answered regarding the role of vascular dysfunction in photoreceptors (PR) degeneration, the causes of vascular dysfunction in RP, as well as the diagnostic, prognostic and perhaps therapeutic potential of measuring ocular haemodynamics in RP patients. While significant evidence supports the theory that vascular dysfunction is associated with but not the cause of PR death in retinitis pigmentosa, evidence suggests that vascular abnormalities in the foveal and parafoveal regions may exacerbate cone cell loss. Additional evidence demonstrates that vascular dysfunction likely results from changes in metabolic demand due to death of PR cells in the retina. Detection and monitoring of ocular blood flow, retinal oxygen saturation, endothelin-1 levels and vascular structural abnormalities could provide diagnostic, prognostic and therapeutic potential for patients with RP.

To evaluate the inter-device reproducibility of retrobulbar blood flow measurements obtained by two commercially available CDI (color Doppler imaging) devices.The right eyes of 10 healthy volunteers were investigated. Four examiners, namely two ophthalmologists and two radiologists, performed CDI examination of the ophthalmic artery, central retinal artery and temporal short posterior ciliary arteries using both CDI devices: ESAOTE MYLAB™ and SIEMENS ANTARES STELLAR PLUS™. The peak systolic velocity (PSV), the end-diastolic velocity (EDV) and the resulting resistivity index (RI) were averaged for 3 cardiac cycles. To evaluate the reproducibility between both device measurements, the Lin's concordance correlation coefficient (CCC) was used. CCC can be expressed as the product of Pearson's r (the measure of precision) and C_b (the measure of accuracy).Results show that the inter-device reproducibility for CDI measurements is not acceptable since a poor degree of overall concordance (0.15CCC0.37) was obtained: accuracy was high (C_b 0.71) but overall precision low (0.18Pearson's r0.47). Ophthalmologists and radiologists obtained similar results.To evaluate the causal role of blood flow abnormalities in glaucoma, CDI analysis using different devices seems unreliable. CDI inter-device reproducibility seems unrelated to medical speciality of the examiners. However, to improve present results, the use of similar probes and standardized CDI instrument settings as well as a CDI images analysis by a single grader, might possibly improve the inter-device reproducibility when testing the retrobulbar blood flow velocity.Valutare la riproducibilità delle misurazioni delle velocità di flusso ematico nei vasi retrobulbari di volontari sani: le misurazioni sono state ottenute con due diverse strumentazioni ecografiche commercialmente disponibili.Quattro operatori, due radiologi e due oculisti, hanno misurato le velocità di flusso nell’arteria oftalmica (AO), nell’arteria centrale della retina (ACR) e nelle arterie ciliari posteriori brevi (ACPB) in 10 occhi di volontari sani utilizzando due ecografi: ESAOTE MYLAB™ and SIEMENS ANTARES STELLAR PLUS™. Sono state calcolate le medie di 3 cicli cardiaci dei parametri di flusso PSV (velocità di picco sistolico), EDV (velocità di fine diastole) e IR (indice di resistività). Per valutare la riproducibilità delle misure effettuate con le due strumentazioni è stato calcolato il coefficiente di correlazione di Lin (CCC). Il CCC può essere espresso come il prodotto del coefficiente di Pearson’s r (misura della precisione) e C_b (misura dell’accuratezza).I risultati mostrano che la riproducibilità delle misurazioni tra due ecografi non è accettabile dal momento che è stato ottenuto uno scarso grado di concordanza (0.15CCC0.37): il grado di accuratezza è alto (C_b 0.71) mentre il grado di precisione basso (0.18Pearson’s r0.47). Oculisti e radiologi hanno ottenuto risultati simili.Per valutare il ruolo causale delle anomalie di flusso ematico nella patogenesi della neuropatia ottica glaucomatosa l’utilizzo di diverse strumentazioni ecografiche appare inaffidabile. La riproducibilità delle misurazioni ottenute con diversi macchinari non sembra correlata con la specialità medica dell’esaminatore. L’uso di sonde simili, di settings CDI standardizzati e l’analisi delle immagini da parte di un singolo operatore potrebbero essere accorgimenti adeguati per migliorare i risultati attuali e quindi per migliorare la riproducibilità inter-device delle velocità di flusso nei vasi retrobulbari.

Objective: Analyze the application of the spectral domain optical coherence tomography (SD-OCT), Optovue iVue, on morphofunctional assessment of filtering blebs after different types of glaucoma surgery and point out the correlation between of morphologic features of blebs (bleb-wall thickness, scleral flap profile, and presence of hyporeflective spaces and internal cavity) and intraocular pressure (IOP). Methods: Thirty-eight eyes of thirty-two primarly open angle glaucoma patients, following three different types of glaucoma surgery (trabeculectomy with MMC 0.3%; with the implant of the Ex-PRESS device; with the insertion of Ologen [OLO]) were recruited. Patients attended a 6-month follow-up with intermediate checks at 1 week, 1 month and 3 months. Each visit include the evaluation of bleb using both slit lamp biomicroscopy and OCT. Results: In all patients, regardless of the type of surgery, a very significant reduction of IOP is observed after surgery. The bleb-wall thickness and the scleral flap profile are not shown to be sensitive parameters to identify the functionality of the bleb. The presence of hyporeflective spaces and of a cavity over the sclera is an important sign of bleb functionality. Among the different types of surgery, a higher percentage of blebs provided with hyporeflective spaces is in the Ex-PRESS group. In regards to the presence of a cavity over the sclera, there are no differences between the different groups. Comparing the blebs with filtering aspect at the OCT in the different groups, in the Ex-PRESS group there is a higher percentage of blebs with a filtering aspect compared to the other groups. Conclusions: Optovue iVue, is able to show detailed superficial features of the bleb which significantly correlate with the functionality of the bleb itself.

Background/aims Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4 years. Methods In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4 years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ 2 tests were used to test for baseline blood flow differences between patients who progressed and those who did not progress. Results Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4 years. Conclusions In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years.

Background Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGC) loss and retinal nerve fiber layer (RNFL) injury: this results in functional and morphological changes. The first can be observed by Standard Automated Perimetry (SAP), the second by Optic Coherence Tomography (OCT) that measures the RNFL and ganglion cell complex (GCC) thicknesses. Nevertheless, diagnosis of early glaucoma may be difficult. Recently, Medeiros et al. derived an empirical formula combining the measurement of structural and functional tests to provide an estimate of RGC. The aim of the current study is to analyse the correlation between RGC count, estimated by Medeiros’ formula, and the structural and functional parameters in patients examined for glaucoma and to evaluate SAP, OCT and RGC counts capability to discriminate the weight of the disease itself. Methods Ninety four eyes of 50 consecutive patients clinically referring to glaucoma service of the Universitary Eye Clinic were submitted to a complete ophthalmic evaluation including SAP and Spectral Domain OCT (SD-OCT) of RNFL and macular GCC. Average thickness of RNFL and macular GCC, parameters Global Loss Volume (GLV) and Focal Loss Volume (FLV) over the entire GCC map were taken into account. Estimates of RGC were obtained with the help of a model already published by Medeiros et al. combining light sensitivities from SAP and retinal thickness from OCT. The RGC count was estimated in the entire visual field (central 24°) and in the GCC macular area and then compared with functional and morphological parameters applying Pearson’s correlation coefficient. Results After the classification of the patients by the Glaucoma Staging System 2 of Brusini, we noticed a good correlation among the functional parameters considered, even if the Visual Field Index is unable to identify early glaucoma. An analogous result can be observed for structural data (RNFL and GCC). The correlation detected between functional and structural parameters was moderate. Great differences in RGC counts were found between groups at various stages of glaucoma. GLV showed highest level of correlation (r > −0.8) with RCG counts. Conclusions Estimate circumpapillary and macular RGC counts can discriminate various stages of the disease and there is also a good/very good correlation with both functional and structural parameters. GLV could be used instead of RGC counts in clinical practice. Electronic supplementary material The online version of this article (doi:10.1186/s12886-015-0177-x) contains supplementary material, which is available to authorized users.

This study was done to evaluate the intra- and inter-operator reproducibility of colour Doppler imaging (CDI) in assessing blood flow velocity in the ophthalmic (OA), central retinal (CRA) and short posterior ciliary arteries (SPCA) in healthy subjects. The right eye of two groups of eight healthy volunteers was examined. Two radiologists and two ophthalmologists, divided into pairs, measured peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) of each vessel using a different CDI device for each group. The concordance between two measurements was evaluated with Lin’s concordance correlation coefficient (CCC). Globally, very good degrees of intra-operator concordance were obtained for the PSV (0.859 cm/s), EDV (0.834 cm/s) and RI (0.859) of the OA. There was moderate concordance for PSV (0.574 cm/s) and EDV (0.594 cm/s) and good concordance for RI (0.694) for the CRA. Good degrees of concordance were obtained for the SPCA measurements. However, inter-operator concordance was found globally poor. These data show that CDI measurements in retrobulbar vessels are operator dependent. To increase the intra-operator and inter-operator concordance, rules should be adopted for timing of the examination and positioning of the probe to minimise the pressure applied on the eye.