Visualization of erythrocyte stasis in the living human eye in health and disease.

Blood cells trapped in stasis have been reported within the microcirculation, but their relevance to health and disease has not been established. In this study, we introduce an in vivo imaging approach that reveals the presence of a previously-unknown pool of erythrocytes in stasis, located within capillary segments of the CNS, and present in 100% of subjects imaged. These results provide a key insight that blood cells pause as they travel through the choroidal microvasculature, a vascular structure that boasts the highest blood flow of any tissue in the body. Demonstration of clinical utility using deep learning reveals that erythrocyte stasis is altered in glaucoma, indicating the possibility of more widespread changes in choroidal microvascular than previously realized. The ability to monitor the choroidal microvasculature at the single cell level may lead to novel strategies for tracking microvascular health in glaucoma, age-related macular degeneration, and other neurodegenerative diseases.

Predictors of intraocular pressure reduction after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a prospective trial.

PURPOSE: To evaluate the association between postoperative intraocular pressure (IOP) reduction and phacoemulsification parameters in patients who underwent both conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a prospective multicenter comparative study that enrolled 90 participants who underwent cataract surgery at the University of Maryland Medical System and the Wilmer Eye Institute. Patients underwent FLACS in one eye and CPS in the fellow eye. IOP was measured prior to surgery and monitored through six months postoperatively. Demographic, clinical, biometric, and intraoperative variables including cumulative dissipated energy (CDE), aspiration time, and phacoemulsification time were analyzed for any significant association with postoperative IOP. Postoperative IOP reduction was the primary outcome variable. A secondary goal of the study was to determine differences in postoperative IOP reduction between CPS and FLACS cohorts. RESULTS: In total, 157 non-glaucomatous eyes were included. Using multivariable analysis, we found preoperative IOP to be consistently associated with postoperative IOP reduction in the entire cohort. At the 6-month follow-up visit, there was a 12.4% reduction in IOP (-2.2 ± 3.4 mm Hg) seen, with no statistically significant difference between FLACS and CPS (12.3% ± 19.4% vs 12.5% ± 19.3%, respectively, p = 0.32). FLACS reduced the CDE required for phacoemulsification (6.6 ± 4.4%-seconds vs 8.6 ± 6.9%-seconds, respectively, p < 0.05). CDE was a predictor of IOP response at 6 months, but subgroup analysis revealed that this trend was driven by seven eyes requiring high CDE, and for the majority of eyes, CDE did not influence the size of the decrease. The seven eyes experiencing highest CDE were less likely to show IOP reduction at 6 months. CONCLUSION: Both FLACS and CPS resulted in similar and significant IOP reductions through 6 months after surgery. Preoperative IOP was significantly associated with IOP reduction, and CDE generally did not influence the size of the decrease.

A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry.

Purpose: The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. Methods: This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. Results: In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (ß = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (ß = -21.1%, P = 0.03), and White race (ß = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Conclusions: Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. Translational Relevance: The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

ANGIOGRAPHIC SMOKESTACK LEAKAGE NOT ASSOCIATED WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report a series of cases with smokestack leakage on fundus fluorescein angiography outside the clinical setting of central serous chorioretinopathy. METHODS: A multicenter, observational retrospective case series evaluating fundus fluorescein angiography on Topcon and Optos systems. RESULTS: Seven patients with neovascularization due to ischemic retinopathy demonstrated a unique smokestack pattern of angiographic leakage. The patients' ages ranged between 44 and 71 years and were seen at 3 academic teaching hospitals in the Washington-Baltimore metropolitan area. Five patients had been diagnosed with proliferative diabetic retinopathy, one with sickle cell ischemic retinopathy, and one with branch retinal artery occlusion; none of the patients had a known history or clinical signs of current or past central serous chorioretinopathy. CONCLUSION: This is the first published case series to the author's knowledge of ischemic retinopathy displaying a smokestack leakage pattern on fundus fluorescein angiography that is classically described with idiopathic central serous chorioretinopathy.

Dexamethasone implant migration in an eye with congenital glaucoma: A case report and review of the literature.

INTRODUCTION: The dexamethasone (DEX) implant is an FDA approved treatment for diabetic macular edema, non-infectious posterior uveitis, and macular edema secondary to branch or central retinal vein occlusions. We describe a case of anterior chamber (AC) migration of a DEX implant in a patient with a history of congenital glaucoma and perform a review of the literature on this particular complication, summarizing the common risk factors, subsequent complications, and management options. CASE DESCRIPTION: A 46-year-old female with a history of congenital glaucoma, status post cataract extraction with insertion of intraocular lens, pars plana vitrectomy, and Baerveldt tube implant in the left eye was referred for post-operative cystoid macular edema (CME). The patient underwent insertion of a DEX implant, resulting in improvement in her CME. After the fourth implant was injected, the patient noticed a white line in her eye while looking in the mirror after doing jumping jacks. Slit lamp examination confirmed migration of the implant into the AC. Ultimately, the patient was taken to the operating room, where her implant was removed via bimanual vitrectomy through an anterior approach. CONCLUSION: This case report and literature review explores the ophthalmic structural changes specific to congenital glaucoma which may have predisposed this eye to anterior migration of the DEX implant. The purpose of this review is to detail the anatomic changes that may increase the risk of anterior chamber implant migration in patients with congenital glaucoma so that physicians may be aware of these risks when selecting patients for this implant.

Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry.

Changes in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44-9.68%). Intervisit variability was 4.85% (range 0.15-8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.

Referral to Low Vision Services for Glaucoma Patients: Referral Criteria and Barriers.

PURPOSE: To determine what criteria are being used by glaucoma specialists to refer patients to low vision services (LVS) and to identify potential barriers to LVS referral. METHODS: A survey was emailed to members of the American Glaucoma Society (AGS). The number and percentage of responses to each survey question were examined. RESULTS: Reported criteria for referral included difficulty performing activities related to vision (78%), degree of visual field loss (63%), and difficulty with orientation and mobility (27%). Reported barriers to LVS referral included patients not expressing difficulty with activities related to vision (34%), not having enough time to counsel patients during clinic visits (32%), and perceiving that patients would not be able to afford LVS even if they were referred (31%). CONCLUSIONS: Among glaucoma specialists, patient-reported difficulties with vision-related activities were the most common criteria used for LVS referral. Reported barriers to LVS referral, including perceived patient economic restraints and insufficient time to counsel patients during clinic visits, need to be addressed through appropriate interventions.

Nonmedical Out-of-Pocket Patient and Companion Expenditures Associated With Glaucoma Care.

PURPOSE: Nonmedical out-of-pocket cost to both patients and their companions of office visits for routine glaucoma care has not been extensively studied in the United States. We evaluate potential key predictors of patient expenditures that are critical to assessing the cost-effectiveness of glaucoma health care delivery. MATERIALS AND METHODS: In total, 300 patients responded to the survey in 3 clinics in 2 clinical practice settings. Main outcome measures included both average visit and yearly expenditures. RESULTS: Of the 300 patients, the majority were female (n=187, 62.3%) and African American (n=171, 57.0%). The median age was 66 years. The median [range; mean (SD)] expenditure per patient visit was $22.10 ($11.1, $42.9; $44.1 (72.8)). Patients with companions paid $38.77 more in average visit expenditure (ß: 0.87, P<0.001). The average visit expenditure for retired patients was $17.37 less when compared with nonretired patients (ß: -0.4, P=0.004). Patients living in a rural or suburban area paid $43.91 and $14.13 more per visit, respectively (ß: 0.73, P=0.0004; ß: 0.31, P=0.03), compared with patients living in an urban area. Patients with noncommercial insurance paid $24.01 less in average visit expenditure (ß: -0.66, P=0.0008). The median yearly patient expenditure was $96.70 [$44.6, $222.7; $210.4 (333.9)]. Patients with companions paid $192.37 more in yearly expenditure (ß: 0.9, P<0.001) than those without companions, whereas retired patients paid $80.83 less in yearly expenditure (ß: -0.39, P=0.03) than nonretirees. Patients with noncommercial insurance paid $109.34 less in yearly expenditure (ß: -0.63, P=0.01). CONCLUSIONS: Although a small part of the total cost of glaucoma care, nonmedical out-of-pocket costs constitute a substantial noncovered medical expense to most patients in the United States. Patients who are employed, come with companions, live in nonurban areas, or are on Medicare have greater expenditures.

Referral to Low Vision Services for Glaucoma Patients: Referral Patterns and Characteristics of Those Who Refer.

PURPOSE: To identify characteristics of ophthalmologists and practices who refer glaucoma patients to low vision services (LVS). MATERIALS AND METHODS: An online survey was distributed to members of the American Glaucoma Society. The survey queried demographics of responders and their clinical practices, criteria and barriers to referral to LVS. Survey responders were categorized as high referrers if they reported referring >5 patients to LVS and low referrers if they referred ≤5. χ and Fischer exact tests were used to compare characteristics between high and low referrers. Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals and determine factors associated with referrer status. RESULTS: High referrers to LVS tended to have >10 patients per month who had already seen a low vision provider (53% vs. 10%, P<0.001), reported following the American Academy of Ophthalmology's Preferred Practice Pattern (PPP) recommendations for LVS referrals (38% vs. 18%, P=0.011), and expressed satisfaction with their current referral practices (86% vs. 70%, P=0.049). In the fully adjusted model those who followed PPP were 2.5 times more likely to report being a high referrer as compared with a low referrer (95% confidence interval, 1.1-5.3). However, only 22% of ophthalmologists reported following these guidelines in their practice. The number of years in practice, practice location or type, volume of patients seen each week, and distance to a low vision clinic were not associated with referral. CONCLUSIONS: Familiarity with PPP guidelines may positively influence LVS referral practices.

A prospective study of early intraocular pressure changes after a single intravitreal triamcinolone injection.

PURPOSE: To prospectively monitor intraocular pressure (IOP) and gonioscopy changes within the first month after a single 4-mg intravitreal injection of triamcinolone acetonide (IVK) (Kenalog, Briston-Meyers Squibb, New York). DESIGN: Prospective comparative interventional case series. METHODS: A consecutive series of 28 eyes of 14 patients with no prior intravitreal injections or history of glaucoma were prospectively enrolled. After baseline evaluation in both eyes, including IOP, gonioscopy, and optic nerve evaluation, a single 4-mg IVK was given in a standard sterile fashion in the eye to be treated. Eyes received IVK for macular edema associated with retinal vein occlusions and in conjunction with photodynamic therapy for choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis, and high myopia. The fellow eye served as the control. After the injection, IOP and gonioscopy were repeated at 1, 2, and 4-week intervals in both eyes. RESULTS: Of the 14 patients, the 5 women and 9 men had a mean age of 67.6 years. Mean baseline IOP of the treated and fellow control eyes were similar at 15.9 versus 16.6 mm Hg, respectively. The control eyes maintained a small IOP range (15.6 to 16.6 mm Hg) during the 1-month follow-up period. In the treated eyes, the mean maximum IOP was 54% above baseline during follow-up, compared with 11% for control eyes. Six of 14 (43%) treated eyes had IOP elevation to 24 mm Hg or higher with mean change of 8.6 mm Hg and a mean maximum IOP of 32.1 mm Hg. There was no correlation between IOP rise and age, sex, diagnosis, or optic nerve appearance. However, during the course of the study, 4 of 6 (67%) of the treated eyes that required topical drops for the IOP elevation had documented abnormal inferior angle changes characterized by pigmented particulate matter in the inferior angle not present at the baseline exam. The most frequent time point for an IOP elevation that required treatment was at 2-week postinjection. No eyes required surgical management of IOP during the course of this 4-week study. CONCLUSIONS: We observed a significant IOP rise in eyes after a single intravitreal injection of 4 mg of triamcinolone within 1 month of injection. In this study, the most frequent time point that required IOP treatment was at 2-week postinjection, suggesting that early and frequent monitoring of IOP should be considered. Two-thirds of eyes that required medical control of IOP developed gonioscopy changes, characterized by particulate matter in the inferior angle, not present at baseline. Eyes that developed gonioscopic changes were 5 times more likely to be treated for IOP elevation than those without gonioscopic findings.

Papilledema associated with dialysis disequilibrium syndrome.

The purpose of this paper is to report a case of dialysis disequilibrium syndrome as an unusual cause of papilledema. A 38-year-old woman with type 1 diabetes mellitus presented with decreased visual acuity and bilateral optic nerve swelling associated with systemic signs and symptoms of dialysis disequilibrium syndrome. Repeated lumbar punctures revealed elevated intracranial pressures. She was placed on acetazolamide with some improvement in symptoms. After renal transplantation, the patient had complete resolution of headaches, nausea and the papilledema. Our conclusion is that patients with visual disturbance and focal neurological symptoms during and after hemodialysis should be suspected of having dialysis disequilibrium syndrome (DDS). DDS is thought to occur as a result of a rapid reduction in plasma osmolality during dialysis. As the shift of urea from cerebral spinal fluid (CSF) is delayed, the relative increase in CSF osmolality draws fluid into the brain. The ensuing cerebral edema is responsible for the characteristic neurological symptoms. We report the association of papilledema with this syndrome, and caution as to the possible concurrent risk of permanent visual impairment.