Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

Purpose: This work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD). Methods: We conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk alleles. Physicians, who were blind to patients' GTGs, obtained patients' AREDS-F use history. The facility performing genetic analysis was blind to the AREDS-F use history. We used logistic analysis to estimate the interaction coefficient between AREDS-F use and GTG 2 vs GTG 3 in a general-population model. Results: The odds ratio of numbers of patients reporting prior AREDS-F use to nonuse for GTG 2 vs GTG 3 was 4.18 (P = .001). Logistic regression, correcting for nongenetic risk factors, gave an estimate of the ß for interaction of AREDS-F with genotype of 1.57 (P = .001). This estimates a corrected odds ratio associated with the effect of interaction of 4.81 between those in GTG 2 compared with those in GTG 3. Conclusions: Our data indicate an interaction between GTGs and AREDS-F use that is consistent in size and direction with previously published reports, which had found that using AREDS-F supplements significantly increases the risk of nvAMD for some users and significantly protects other users.

EFFECT OF SERIAL ANTERIOR CHAMBER PARACENTESIS ON SUSTAINED INTRAOCULAR PRESSURE ELEVATION IN PATIENTS RECEIVING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To investigate the effect of serial anterior chamber (AC) paracenteses in eyes with sustained elevations of intraocular pressure (IOP) in the setting of repeated intravitreal injections (IVI) of anti-vascular endothelial growth factor medications. METHODS: This is a retrospective records review of patients undergoing IVI of anti-vascular endothelial growth factor medication (bevacizumab, ranubizumab, or aflibercept), who demonstrated a sustained elevation of preinjection IOP and also received AC paracentesis immediately after IVI on at least three consecutive visits. Changes in preinjection IOP and cup-to-disk (C:D) ratio were compared before and after the initiation of IVI and before and after the introduction of AC paracenteses with each subsequent IVI. RESULTS: Twenty-three eyes of 17 patients receiving a median of 26 IVI experienced a rise in preinjection IOP from 16.3 mmHg to 21.1 mmHg (P = 0.004) and an increase in mean C:D ratio from 0.37 to 0.47 (P = 0.0002). After introduction of AC paracenteses (median of 12), mean IOP was returned to baseline 16.00 mmHg (P = 0.002), mean C:D ratio stabilized (0.50, P = 0.197), and maximum IOP decreased from 26.8 mmHg to 23.0 mmHg (P = 0.05). Nineteen (82.6%) eyes required an increase in topical glaucoma medications during the study period, and 13 (56.5%) still required additional therapies after initiation of AC paracenteses. Five eyes (38.5%) required laser or glaucoma drainage device procedures. CONCLUSION: Serial AC paracenteses reduced immediate postinjection IOP, and along with standard glaucoma care in most patients, reversed preinjection IOP elevation, and stabilized optic nerve changes associated with repeated intravitreal anti-vascular endothelial growth factor injections in a subset of patients with sustained elevation of preinjection IOP.

An Eye Popping Case of Orbital Necrotizing Fasciitis Treated with Antibiotics, Surgery, and Hyperbaric Oxygen Therapy.

BACKGROUND Necrotizing fasciitis (NF) of the orbit is a rare and deadly condition that requires prompt surgical and medical management to decrease morbidity and mortality.  CASE REPORT Here we present an interesting case of an individual who developed fulminant NF of the left orbit requiring emergent surgical intervention, antibiotics, and subsequent hyperbaric oxygen therapy in an attempt to save the eye.  CONCLUSIONS With an early and aggressive multifaceted approach using antibiotics, surgery, and hyperbaric oxygen it may be possible to preserve eye structure and function. Without treatment NF is a rapidly progressive condition and can result in significant morbidity.

Short-term effects of brimonidine/timolol and dorzolamide/timolol on ocular perfusion pressure and blood flow in glaucoma.

INTRODUCTION: To examine the comparative short-term effects of brimonidine/timolol and dorzolamide/timolol on ocular perfusion pressure and retrobulbar blood flow in patients with primary open angle glaucoma (OAG). METHODS: In a prospective, randomized, double-blind, crossover study, intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), and retrobulbar hemodynamics were assessed in 15 patients with OAG (mean age 68.1 years, eight women) with well controlled IOP. IOP was measured by Goldman applanation tonometery and color Doppler imaging was utilized to assess the retrobulbar blood vessels before and 1 month after treatment with topical brimonidine/timolol and dorzolamide/timolol. Statistical analysis was performed by Friedman two-way analysis of variance by ranks and post-hoc Wilcoxon signed rank test for multiple comparisons with Holm's sequential Bonferroni procedure. P values <0.05 were considered statistically significant. RESULTS: The Friedman test and subsequent post-hoc analysis indicated that IOP, BP, OPP, and retrobulbar blood flow velocities did not significantly differ between brimonidine/timolol and dorzolamide/timolol after 1-month treatment administration in patients with OAG and well controlled IOP. CONCLUSION: In this cohort of patients with OAG, short-term treatment with brimonidine/timolol and dorzolamide/timolol results in similar effects on OPP and retrobulbar blood flow velocities.

Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma.

PURPOSE: To review the role of endothelin in intraocular pressure control, its effect on the trabecular meshwork (TM) and the outflow facility, effect on ocular blood flow and vascular regulation and the potential role of endothelin-1 (ET-1) antagonism in the therapeutic paradigm of glaucoma. METHODS: A thorough review of the medical literature and a meta-analysis on the level of ET-1 in OAG patients in an attempt to demonstrate the evolving importance of endothelin in glaucoma. RESULTS: ET-1 has been identified in the plasma in concentrations that are markedly increased in a number of systemic as well as ocular pathologies such as glaucoma where underlying vascular dysfunction and pathology play a role. It has been shown that ET-1 induces human TM cell contraction in culture and that it can affect the outflow facility. Evidence indicates that systemic ET-1 regulatory mechanisms and vascular responses to it are also altered in glaucoma. Recently, several endothelin antagonists have been shown to have a potential role in glaucoma therapy. In our meta-analysis, only patients with normal tension glaucoma (NTG) (as opposed to patients with high tension glaucoma (HTG)) had significantly higher plasma ET-1 levels compared to non-glaucomatous control. High tension glaucomaHTG patients had significant higher levels of ET-1 in the aqueous humor. CONCLUSIONS: The potential role of ET-1 antagonism in the therapeutic paradigm of glaucoma is an exciting possible new approach in the treatment of OAG patients. In NTG, ET-1 may have both a local and systemic component of vascular dysregulation, while whereas in HTG, the role of ET-1 may be dominantly localized to ocular tissue.

Contrast sensitivity, ocular blood flow and their potential role in assessing ischaemic retinal disease.

PURPOSE: To examine the definition, evaluation methodology, association to ocular blood flow and potential clinical value of contrast sensitivity (CS) testing in clinical and research settings, focusing in patients with ischemic retinal disease. METHODS: A review of the medical literature focusing on CS and ocular blood flow in ischemic retinal disease. RESULTS: CS may be more sensitive than other methods at detecting subtle defects or improvements in primarily central retinal ganglion cell function early on in a disease process. CS testing attempts to provide spatial detection differences which are not directly assessed with standard visual acuity chart testing. Analyzing all studies that have assessed both CS change and ocular blood flow, it is apparent that both choroidal circulation and retinal circulation may have an important role in influencing CS. CONCLUSION: The concept that CS is directly influenced by ocular blood flow is supported by reviewing the studies involving both. Although the studies in the literature have not established a direct cause and effect relationship per se, the literature review makes it logical to assume that changes in retinal and choroidal blood flow influence CS. This raises the possibility that a subjective visual characteristic, specifically CS, may be able to be evaluated more objectively by studying blood flow. It appears appropriate to study the relationship between blood flow and CS more extensively to develop improved ways of measuring various aspects of blood flow to the eye and to best quantify early changes in visual function.

Feasibility of creating a normative database of colour Doppler imaging parameters in glaucomatous eyes and controls.

BACKGROUND AND AIMS: Colour Doppler imaging (CDI) is a frequently cited methodology for quantifying ocular blood flow velocities. This investigation reviews the feasibility of creating a normative database of CDI parameters in glaucoma patients and controls. A literature search was conducted for CDI studies involving glaucomatous eyes. Using data from these studies, a weighted mean was derived for the peak systolic velocity, end diastolic velocity and Pourcelot's resistive index in the ophthalmic, central retinal and posterior ciliary arteries. A multivariate analysis was performed to identify whether methodological characteristics contributed to the inter-study variance in CDI values. Data from 3061 glaucoma patients and 1072 controls were included. The mean values for glaucomatous eyes were within one standard deviation of the values for controls for most CDI parameters. Gender mix (p=0.043), intraocular pressure status (p=0.017), frequency of the ultrasound transducer (p=0.02) and whether the patients were on antihypertensive therapy (p=0.004) contributed to the variance. Methodological differences create inter-study variance in CDI values, complicating the construction of a normative database and limiting its utility. Because the mean values for glaucomatous and normal eyes have overlapping ranges, caution should be used when classifying glaucoma status based on a single CDI measurement.

Update and critical appraisal of combined timolol and carbonic anhydrase inhibitors and the effect on ocular blood flow in glaucoma patients.

Topical hypotensive therapy with both timolol and carbonic anhydrase inhibitors has been shown to be efficacious at reducing intraocular pressure. Many prospective studies have also suggested that carbonic anhydrase inhibitors augment ocular blood flow and vascular regulation independent of their hypotensive effects. Although consistent in their findings, these studies must be cautiously interpreted due to the limitations of study design and specific blood flow imaging modalities. The purpose of this review is to appraise and critically evaluate the current body of literature investigating the effects of combined treatment with topical carbonic anhydrase inhibitors and timolol in patients with glaucoma with respect to ocular blood flow, visual function, and optic nerve head structure.