Cardiac Surgery Patients Have Reduced Vascularity and Structural Defects of the Retina Similar to Persons with Open-Angle Glaucoma.

(1) Background: Growing evidence suggests impairment of ocular blood flow in open-angle glaucoma (OAG) pathology, but little is known about the effect of an impaired cardiovascular supply on the structural and vascular parameters of the retina. This study aims to investigate the variations of these parameters in OAG patients compared to patients undergoing cardiac surgery (CS) with cardiopulmonary bypass. (2) Methods: Prospective observational study with 82 subjects (30 controls, 33 OAG patients, and 19 CS patients) who underwent ophthalmological assessment by swept-source OCT and CDI in one randomly selected eye. (3) Results: In the CS group, OA and SPCA PSV and EDV were significantly lower, OA and SPCA RI were significantly higher compared to the OAG and healthy subjects (p = 0.000-0.013), and SPCA EDV correlated with linear CDR (r = -0.508, p = 0.027). Temporal ONH sectors of GCL++ and GCL+ layers in the CS group did not differ significantly compared to the OAG patients (p = 0.085 and p = 0.220). The CS patients had significantly thinner GCL++ and GCL+ layers in the inner sectors (p = 0.000-0.038) compared to healthy subjects, and these layers correlated with the CRA PSV, EDV, and RI and SPCA PSV (p = 0.005-0.047). (4) Conclusions: CS patients had lower vascular and structural parameters in the ONH, and macula compared to the healthy controls that were similar to persons with OAG.

Changes in Macular Thickness after Cataract Surgery in Patients with Open Angle Glaucoma.

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.

Disease progression pathways of wet AMD: opportunities for new target discovery.

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among people age 60 years or older in developed countries. Current standard-of-care anti-vascular endothelial growth factor (VEGF) therapy, which inhibits angiogenesis and vascular permeability, has been shown to stabilize choroidal neovascularization and increase visual acuity in neovascular AMD. However, therapeutic limitations of anti-VEGF therapy include limited durability with consequent need for frequent intravitreal injections, and a ceiling of efficacy. Current strategies under investigation include targeting VEGF-C and VEGF-D, integrins, tyrosine kinase receptors, and the Tie2/angiopoietin-2 pathway. A literature search was conducted through November 30, 2021 on PubMed, Medline, Google Scholar, and associated digital platforms with the following keywords: wet macular degeneration, age-related macular degeneration, therapy, VEGF-A, VEGF-C, VEGF-D, integrins, Tie2/Ang2, and tyrosine kinase inhibitors. AREAS COVERED: The authors provide a comprehensive review of AMD disease pathways and mechanisms involved in wet AMD as well as novel targets for future therapies. EXPERT OPINION: With novel targets and advancements in drug delivery, there is potential to address treatment burden and to improve outcomes for patients afflicted with neovascular AMD.

Changes in ocular morphology after cataract surgery in open angle glaucoma patients.

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.

Anterior segment optical coherence tomography imaging and ocular biometry in cataract patients with open angle glaucoma comorbidity.

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.

Ocular side effects of target therapy and immunotherapy in patients with cutaneous malignant melanoma.

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.

Review of non-invasive intracranial pressure measurement techniques for ophthalmology applications.

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.

Waveform parameters of retrobulbar vessels in glaucoma patients with different demographics and disease severity.

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 < 0.001) and central retinal artery period (p = 0.016). No statistical differences were found in regard to race, diabetes status, glaucoma family history, and smoking. 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.

Management of Glaucoma in Pregnancy.

Management of glaucoma during pregnancy represents a challenge for the physician. Important disease and patients' health decisions begin even before conception and continue throughout pregnancy and breastfeeding. The data on this topic is limited due to ethical and legal constraints and challenges of conducting large, prospective, and randomized clinical trials on this patient population. Our review suggests that individually, intraocular pressure is lower in a pregnant woman when compared with a nonpregnant woman. Importantly, the medical management of glaucoma during pregnancy poses special challenges due to the possibility of adverse effects of medications on the fetus and newborn. Laser trabeculoplasty and traditional filtration surgery, and minimally invasive glaucoma surgery, represent nondrug management options. Thus, managing glaucoma in pregnancy is a delicate balance between treatment to prevent damage to the optic nerve in the mother and avoidance of interventions potentially harmful to the fetus. This literature review of published individual and population-based studies was performed to explore current knowledge and guidelines in the management of glaucoma in pregnancy.

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery.

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema. Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious. Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

Effects of Sex Hormones on Ocular Blood Flow and Intraocular Pressure in Primary Open-angle Glaucoma: A Review.

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 effects of antioxidants on ocular blood flow in patients with glaucoma.

PURPOSE: To investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open-angle glaucoma (OAG). METHODS: Forty-five patients with confirmed OAG were enroled in a randomized, double blinded, placebo-controlled cross-over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non-invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t-tests, with p < 0.05 considered statistically significant. RESULTS: Antioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non-active retina capillaries compared to placebo. CONCLUSION: One-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG.

Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance.

PURPOSE: This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. METHODS: A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. RESULTS: The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. CONCLUSIONS: The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics.

Generic medications in ophthalmology.

The purpose of this review is to discuss the process of genericisation of medications in the US and Europe with a focus on ophthalmic drugs. Regulatory guidelines of the US Food and Drug Administration and the European Medicines Agency will be discussed, and the advantages and concerns of genericisation will be explored. We will look at various studies concerning the safety and efficacy of generic drugs compared to their branded counterparts. In particular, the challenges of assuring bioequivalence and therapeutic equivalence in topical ophthalmic drugs will be examined.

In vitro simulation of the first technique for non-invasive measurement of volumetric ophthalmic artery blood flow in humans.

BACKGROUND AND OBJECTIVE: To evaluate the accuracy, reproducibility, and variability of volumetric flow measurements taken by color Doppler imaging ultrasound, using an in vitro "phantom" model to simulate the ophthalmic artery. MATERIALS AND METHODS: An agar flow phantom with two wall-less lumens was constructed to simulate the ophthalmic artery. Velocity and volumetric flow measurements were taken for various flow rates and ultrasound probe positions. The measurements were analyzed for accuracy, reproducibility, and variability. RESULTS: Velocity measurements were more accurate than flow measurements (8 of 24 vs 3 of 24 accurate trials). The average coefficient of variation for volumetric blood flow was 11.4% (n = 120). Volumetric flow significantly correlated with velocity (R(2) = 0.408, n = 600, P < .001). The highest correlation was achieved using the large lumen with the probe held at 75 degrees , offset to the flow (R(2) = 0.862, n = 75). CONCLUSION: Based on an in vitro model, non-invasive color Doppler imaging recordings of volumetric flow measurements in the ophthalmic artery significantly correlated with velocity and higher correlations were found using the larger lumens, although the data showed a lack of high accuracy in measurements of flow and velocity.

The effects of raloxifene hydrochloride on ocular hemodynamics and visual function.

OBJECTIVE: To assess the comprehensive effects of raloxifene hydrochloride on retinal, choroidal and retrobulbar hemodynamics and on visual function in post-menopausal women. DESIGN: Twenty-four post-menopausal women (age 55 +/- 3.8 years) were recruited for this cross-sectional study: 12 received placebo and 12 received raloxifene hydrochloride 60 mg once a day for 3 months. Baseline measurements of both groups included heart rate (HR), blood pressure (BP), visual acuity, contrast sensitivity and intraocular pressure (IOP) for both eyes. A comprehensive ocular blood flow (OBF) assessment was obtained for each patient in a randomly chosen study eye. Retinal blood flow data was obtained using confocal scanning laser Doppler flowmetry [Heidelberg Retinal Flowmeter (HRF)]. Color Doppler imaging (CDI) was used to assess retrobulbar hemodynamics in the ophthalmic, central retinal, short nasal and temporal posterior ciliary arteries. Baseline vision and hemodynamics in post-menopausal subjects were compared using paired Student's t tests, and the percentage change in baseline versus 3-month parameters was analyzed. RESULTS: There were no statistically significant differences between 3 months of raloxifene therapy and placebo in terms of age, HR, arterial or mean BP, visual acuity, contrast sensitivity, IOP or retinal or retrobulbar blood flow. CONCLUSION: Raloxifene therapy at 60 mg/day had no clinically significant impact on BP, IOP or OBF in post-menopausal women.

Dye dependent differences in arteriovenous passage times: a comparison of indocyanine green and fluorescein sodium dye analysis.

BACKGROUND AND OBJECTIVE: To evaluate the difference in arteriovenous passage time calculated from retinal angiograms using indocyanine green and fluorescein sodium dye in healthy individuals. PATIENTS AND METHODS: Examinations of eight healthy individuals (mean age +/- standard deviation: 27.3 +/- 4.2 years) who had four consecutive ophthalmic visits that were 2 weeks apart were analyzed. Indocyanine green and fluorescein angiography were performed sequentially (with the indocyanine green angiography occurring first) using scanning laser ophthalmoscopy. Arteriovenous passage times were calculated offline using digital angiogram video analysis. RESULTS: Mean arteriovenous passage times calculated from indocyanine green angiography (1.417 +/- 0.136 seconds) recordings were significantly shorter than fluorescein sodium times (2.539 +/- 0.421 seconds) (P < .0001) and intra-group variability was similar. There were no significant correlations between indocyanine green and fluorescein sodium arteriovenous passage times. CONCLUSION: Arteriovenous passage times calculated using indocyanine green and fluorescein angiography are not interchangeable.

The relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration. PATIENTS AND METHODS: Thirteen patients with age-related macular degeneration were assessed by both color Doppler imaging and scanning laser ophthalmoscope indocyanine green (ICG) angiography. Color Doppler imaging was used to measure peak systolic and end diastolic velocity (from which the resistance index, a measure of the resistance to flow downstream, was calculated) in the retrobulbar vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area dilution analysis for quantitative choroidal fluorescence intensity assessment. Color Doppler imaging parameters were correlated with scanning laser ophthalmoscope ICG area dilution analysis parameters. RESULTS: A good correlation was found between the posterior ciliary arteries resistance index and scanning laser ophthalmoscope ICG area dilution analysis fluorescence duration. CONCLUSIONS: Scanning laser ophthalmoscope ICG area dilution analysis "duration" may serve as an alternative to color Doppler imaging in assessing the resistance to blood flow in the posterior ciliary arteries.