Angelica Cerulli

Optic Nerve and Optic Radiation Neurodegeneration in Patients with Glaucoma: In Vivo Analysis with 3-T Diffusion-Tensor MR Imaging

PURPOSE To evaluate, with high-field-strength diffusion-tensor (DT) magnetic resonance (MR) imaging, the axonal architecture of the optic nerves and optic radiations in patients with glaucoma and determine whether DT MR imaging-derived parameters correlate with disease severity. MATERIALS AND METHODS The study was approved by the institutional review board. All participants provided written informed consent. Sixteen patients with primary open-angle glaucoma were examined. Glaucoma severity was clinically assessed with use of a six-stage system based on static threshold visual field parameters. Ten healthy individuals served as control subjects. DT MR imaging was performed with a 3-T MR unit. Mean diffusivity (MD) and fractional anisotropy (FA) maps were automatically created. Regions of interest were positioned on the MD and FA maps, and mean MD and mean FA values were calculated for each optic nerve and each optic radiation. RESULTS The optic radiations and optic nerves of patients with glaucoma, as compared with control subjects, had significantly higher MD and significantly lower FA. The mean MD values for the optic nerves and the glaucoma stages varied consistently (r = 0.8087, P < .0001). A negative correlation between mean FA for the optic nerves and glaucoma stage (r = -0.7464, P < .0001) was observed. CONCLUSION Glaucoma is a complex neurologic disease that affects optic nerves and optic radiations. The finding that DT MR imaging-derived MD and FA in the optic nerves correlate with glaucoma severity suggests that these parameters could serve as complementary indicators of disease severity.

Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects.

Certain general conclusions can be drawn from a series of 56 studies on glaucoma prevalence. Even in the most recently published studies the rate of undiagnosed glaucoma is particularly high. Another fairly constant finding is the discrepancy between the clinical and epidemiologic diagnoses of glaucoma. The prevalence of primary open-angle glaucoma (POAG) has been increasing, and this trend is undoubtedly due at least in part to advances in diagnostic technology. The decreasing prevalence of primary angle-closure glaucoma (PACG) is due to the adoption of more stringent criteria for the diagnosis of this form of glaucoma. Prevalence increases proportionately with age for each racial group. African or African origin populations had the highest POAG prevalence at all ages but the increase in prevalence of POAG is steeper for white populations. PACG is commonest in Asian ethnic groups, with the exception of the Japanese. Low-tension glaucoma (LTG) is quite common in the Japanese population. Over 80% of those with PACG live in Asia, while POAG disproportionately affects those of African derivation. Women are more affected by glaucoma. Very few incidence studies have been completed, because the cost of examining large samples is high. There are only two recent studies conducted on persons of African descent in Barbados (West Indies) and on white inhabitants of Rotterdam (Netherlands). Risk of incident glaucoma was highest among persons classified as having suspect POAG at baseline, followed by those with ocular hypertension. No difference in incidence of POAG between men and women was found. The more recent studies which included routine visual-field testing reveal rates of blinding glaucoma <10% in many countries, including those that are developing.

Retinal damage caused by high intraocular pressure-induced transient ischemia is prevented by coenzyme Q10 in rat.

Recent studies support a role for excitotoxicity in the development of retinal ganglion cell (RGC) damage in subjects suffering from glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection, preventing the formation of the mitochondrial permeability transition pore. Using an established animal model of retinal ischemia/reperfusion here, we show that synaptic glutamate increases at 130min from beginning of reperfusion and delayed apoptosis in the RGC layer is seen at 24h. Intraocular administration of CoQ10 minimizes glutamate increase and affords neuroprotection, suggesting that oxidative stress and energy failure might be implicated in the mechanisms of RGC death.

Validity and limits of the rebound tonometer (ICare®): clinical study.

Purpose The aim of this study was to evaluate the measurement of intraocular pressure (IOP) using a new induction/impact rebound tonometer (ICare®) compared with Goldmann applanation tonometry (GAT). We also aimed to quantify the systematic and random errors (bias) of the 2 methods, to evaluate the sensitivity and specificity of the ICare® tonometer in identifying patients with 21 mmHg or more measured with the GAT, and to study the influence of corneal thickness on IOP measurement with the 2 tonometers. Methods We compared the IOP values obtained with the 2 instruments in 97 patients. Results Analysis based on the Bland and Altman method revealed that the IOP values recorded with the ICare® tonometer were slightly higher than those obtained with the GAT. The estimated bias for right eye measurements was 0.78 mmHg with 95% limits of agreement ±3.55 mmHg. This overestimation, which is not clinically relevant, was confirmed when we used the IOP values corrected according to central corneal thickness for data analysis. The sensitivity and specificity were 0.90 and 0.95, respectively. Conclusions The ICare® tonometer proved to be comparable with other nonconventional tonometers and can be used by nonophthalmologists and paramedical personnel during screening tests of populations. In addition, the ICare® tonometer could be considered a valid alternative to GAT when GAT is not available.

Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection.

Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimers and Parkinsons diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.

The 12-year incidence of glaucoma and glaucoma-related visual field loss in Italy: the Ponza eye study.

PurposeTo assess the 12-year incidence of glaucoma and glaucoma-related visual field loss in a population-based cohort study. PatientsIn 2000, we reexamined 411 of the 581 survivors from the original Ponza eye study conducted in 1988. MethodsPrimary open-angle (POAG), primary angle-closure (PACG), and secondary [pseudoexfoliative (PEX)] glaucoma were diagnosed according to the 3-tiered system of evidence developed by the International Society of Geographical and Epidemiological Ophthalmology. Severity of glaucoma was classified according to the Bascom-Palmer system. Visual loss was defined according to World Health Organization guidelines. Relative risk ratios were calculated for several variables. ResultsThe 12-year incidence of definite POAG was 3.8% (95% confidence intervals (CI), 2.3-6.2), that is, an average annual rate of 0.32%. Corresponding rates for PACG and PEX glaucoma were 0.5% (95% CI, 0.1-1.8) and 0.8% (95% CI, 0.3-2.2), respectively. Half the incident glaucoma cases (45%) had not been diagnosed earlier. Fifty-five percent of the incident POAG eyes had Bascom-Palmer stage 1 or 2 disease and 40% of the incident PACG or PEX glaucoma eyes had stage 3 or 4 disease. Seven of 20 incident glaucoma cases presented with monocular or binocular visual loss because of advanced visual field loss. Significant risk factors for POAG included high myopia (>6.0 D), intraocular pressure ≥22 mm Hg, and glaucoma family history. ConclusionThe average annual incidence of definite POAG in Ponzas lower than that reported in persons of African ancestry and higher than that observed in certain other white populations.

Association Between Alzheimer's Disease and Glaucoma: A Study Based on Heidelberg Retinal Tomography and Frequency Doubling Technology Perimetry

Aim: To assess the frequency of glaucoma-like alterations in Alzheimers disease (AD) patients using Heidelberg Retinal Tomograph III (HRT-3) and Frequency Doubling Technology (FDT) perimetry. Methods: The study included 51 eyes of 51 AD subjects and 67 eyes of 67 age- and sex-matched controls. Subjects underwent an ophthalmological examination including measurements of intraocular pressure (IOP), Matrix FDT visual field testing, optic nerve head morphology and retinal nerve fiber layer thickness (RNFLt) assessment by slit-lamp biomicroscopy and HRT-3. Results: The frequency of alterations was significantly higher in the AD group (27.5 vs. 7.5%; p = 0.003; OR = 4.69). AD patients showed lower IOP (p = 0.000) despite not significantly different values of central corneal thickness (CCT) between the groups (p = 0.336). Of all the stereometric parameters measured by HRT-3, RNFLt was significantly lower in AD patients (p = 0.013). This group also had significantly worse results in terms of Moorfields Regression Analysis (p = 0.027). Matrix showed significantly worse Mean Deviation (MD) (p = 0.000) and Pattern Standard Deviation (PSD) (p = 0.000) values and more altered Glaucoma Hemifield Test (p = 0.006) in AD patients. Pearsons R correlation test showed that Mini Mental State Examination is directly correlated with MD (R = 0.349; p = 0.034) and inversely correlated with PSD (R = −0.357; p = 0.030). Conclusion: Patients with AD have a higher frequency of glaucoma-like alterations, as detected by the use of HRT-3. These alterations were not associated with elevated IOP or abnormal CCT values.

Evaluation of eye movements pattern during reading process in patients with glaucoma: a microperimeter study

Purpose To assess eye movements pattern during reading process in patients with primary open-angle glaucoma (POAG) using a microperimeter. Methods Thirty-two patients with POAG at early and moderate stage, according to Glaucoma Staging System 2, and 34 healthy age- and sex-matched subjects were included in the study. Reading speed and accuracy were previously evaluated with specific tests adjusted for age. In addition, all participants performed a reading test with Microperimeter Nidek MP1. Ocular movements during the reading process were recorded and values of maximum and minimum eye movements along the horizontal (Xmax and Xmin) and vertical (Ymax and Ymin) axis and mean ocular movement speed were provided by the MP1. Results There were significant differences between patients with and without POAG in terms of Xmax and Ymax eye movement values (4.75 ± 2.57 versus 3.38 ± 0.67, p = 0.003; and 4.39 ± 1.43 versus 3.34 ± 0.52, p<0.001, respectively). These differences were significant even comparing only stage 1 patients to controls. There were no significant differences in Xmin and Ymin values and mean ocular movement speed between the 2 groups. Conclusions The study showed significant differences in eye movements pattern in patients with POAG during the reading test performed with the MP1 when compared to the control group. These alterations may be partly the consequence of the neurodegenerative process of the central visual pathway in glaucoma.

Nationwide Incidence of Endophthalmitis Among the General Population and the Subjects at Risk of Endophthalmitis in Italy

Purpose: To investigate the incidence of endophthalmitis in Italy. Methods: The Ministry of Health Hospital Admissions online database was searched to identify cases of endophthalmitis and cases with risk factors for endophthalmitis (corneal ulcer, open wound of the eyeball, and intraocular surgery including retinal, iris, and lens procedures with or without vitrectomy). Annual Incidence rates (overall, and age- and gender-specific) were computed in the general population and in the population with one or more of the risk factors for endophthalmitis. Results: The overall annual incidence of endophthalmitis / 100,000 inhabitants was 2.0 (95% confidence interval (CI):1.8–2.1) in 2003. The risk for endophthalmitis and for most factors that cause predisposition to endophthalmitis was higher in males. The annual incidence rates of corneal ulcer, open wounds of the eyeball, retinal procedures, iris procedures, lens procedures, and other intraocular procedures were respectively (per 100,000 inhabitants) 4.6, 4.8, 43.0, 9.2, 775.7, and 63.0. The annual incidence of endophthalmitis per 100,000 predisposed subjects was 220 (95% CI: 210–230), and the risk was higher in males (relative risk 1.7, 95% CI: 1.5–1.9). Annual incidence rates remained stable from 1999 to 2003. Conclusions: Higher rates of open wounds of the eyeball, corneal ulcers, and retinal surgery among males may be responsible for their higher risk for endophthalmitis.

The Aging of the Choroid

The first section of this chapter describes the anatomy and the physiology of the choroid and the vascular pattern of the choroidal vessels. The choroid is of fundamental importance for nourishment of the retina so that all the alterations of the choroid lead to a disfunction of the retinal pigment epithelium (RPE), Bruchs membrane, and choriocapillary complex. The various methods used to study the choroid and its pathologies in post-mortem studies and in vivo are described—injection of chromopolimer, Indocyanine Green Angiografy, and Doppler flow studies. Age-related changes of choroid are analyzed. Alterations have been described in the various layers of the choroid, which are part of the physiologic aging process. In certain cases, they can cause disease, but sometimes the border between physiologic and pathologic age-related changes is very hard to identify. The choroid represents the preferential target of certain age-related diseases. In particular, we describe the physiopathology of age-related pathologies such as hypertension, diabetes, AMD, and atherosclerosis—so common in the elderly. In particular, diabetes and AMD represent the main causes of blindness in industrialized countries.