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.

Raman microspectroscopy analysis in the treatment of acanthamoeba keratitis.

Acanthamoeba keratitis is a rare but serious corneal disease, often observed in contact lens wearers. Clinical treatment of infected patients frequently involves the use of polyhexamethylene biguanide (PHMB), a polymer used as a disinfectant and antiseptic, which is toxic also for the epithelial cells of the cornea. Prompt and effective diagnostic tools are hence highly desiderable for both starting early therapy and timely suspension of the treatment. In this work we use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in cystic phase. In particular, we investigate the effect of PHMB at the single-cell level, providing useful information on both the underlying biochemical mechanism and the time frame for Acanthamoeba eradication in ocular infections. Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard multivariate analysis methods, allows discriminating between live and dead Acanthamoebas, which is fundamental to optimizing patients' treatment.

Efficacy of Timolol 0.1% Gel and a Prostaglandin Analog in an Unfixed Combination Compared to the Corresponding Fixed Combinations.

PURPOSE: To investigate the intraocular pressure (IOP) reduction with prostaglandin analogs (PGAs)-timolol fixed combinations versus the unfixed combination of the same PGAs and timolol 0.1% in gel-forming carbomer. METHODS: Patients with primary open-angle glaucoma (POAG) receiving for at least 4 weeks the fixed combinations of PGA-timolol, administered once a day in the evening (0.005% latanoprost with 0.5% timolol, 0.004% travoprost with 0.5% timolol, 0.03% bimatoprost with 0.5% timolol) were switched to an unfixed combination of the same PGA (once a day in the evening) with timolol 0.1% in gel-forming carbomer (once a day in the morning) for at least 4 weeks. The primary endpoint was to compare efficacy of fixed vs unfixed combinations in lowering IOP. The effects of both regimens on short-term IOP fluctuations were also assessed. RESULTS: A total of 32 patients (64 eyes) fulfilled inclusion criteria: 17 patients received latanoprost-timolol fixed combination, 9 travoprost-timolol fixed combination, 6 bimatoprost-timolol fixed combination. For all considered time periods each unfixed combination induced an IOP reduction significantly higher than the corresponding fixed combination (paired t test: p<0.05 in all measurements). The diurnal IOP reduction was significantly higher during the unfixed combinations (p<0.001). Unfixed combinations significantly decreased IOP diurnal fluctuations and increased the percentage of patients with daily IOP fluctuation ≤2 mm Hg. CONCLUSIONS: In this pilot study, PGA and timolol seems to be more effective in POAG treatment when administered as unfixed combinations, reducing both IOP and daily fluctuations. The once a day timolol 0.1% gel-forming carbomer may be a valuable option in PGA-timolol unfixed combination regimen.

Brain involvement in glaucoma: advanced neuroimaging for understanding and monitoring a new target for therapy.

On the basis of a large body of experimental data the notion that glaucoma damages retinal ganglion cells and central areas of the visual system has been put forward. The mechanisms underlying glaucomatous involvement of the central areas are not known: the most likely hypothesis is that this event is the result of an anterograde transynaptic neurodegeneration triggered by ganglion cells' death. However, it is possible that in some cases it may be the consequence of a neurodegenerative disease of the central nervous system. In any event, novel mechanisms leading to cell demise might be implicated. The development of powerful neuroimaging techniques in conjunction with sophisticated analysis has recently provided compelling support to the involvement of central stations of the visual pathway in patients suffering of glaucoma. Diffusion Tensor-MRI allows the central damage associated with glaucoma to be assessed and therapeutic efficacy of novel neuroprotective interventions to be quantified.

Glaucoma progression associated with Leber's hereditary optic neuropathy.

The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

Anatomical and functional results of macular hole retinal detachment surgery in patients with high myopia and posterior staphyloma treated with perfluoropropane gas or silicone oil.

PURPOSE: To evaluate the use of perfluoropropane gas (C3F8) versus silicone oil (SO) for retinal detachment secondary to macular hole in patients with high myopia and posterior staphyloma. METHODS: In a retrospective study, 30 eyes of 30 patients underwent pars plana vitrectomy, and C3F8 (17 patients) or SO (13 patients) tamponade; internal limiting membrane peeling was performed successfully at the first surgery in 23 patients. High-density silicone oil tamponade was used for reoperations. RESULTS: The mean values of patients' characteristics were as follows: age, 57.7 years; axial length, 29.02 mm; spherical equivalent refraction, -15.40 diopters; initial best-corrected visual acuity, 2.35 logarithm of the minimum angle of resolution; final best-corrected visual acuity, 1.59 logarithm of the minimum angle of resolution. In C3F8 group, best-corrected visual acuity significantly improved (P < 0.001), passing from 2.34 to 1.36 logarithm of the minimum angle of resolution. Vision improvement from blindness to low vision was significantly greater (P = 0.009) in C3F8 group (16 of 17; 94%) than in SO group (6 of 13; 46%). A significant higher initial success (P = 0.025) was found in the C3F8 group (16 of 17; 94%) than in the SO group (7 of 13; 54%). Proliferative vitreoretinopathy was the cause of initial failure; all these subjects achieved anatomical success after being reoperated with high-density silicone oil tamponade. CONCLUSION: C3F8 and internal limiting membrane peeling could represent the most effective strategy in highly myopic patients with macular hole retinal detachment. Other tamponade agents must be investigated.

Treating retinal vein occlusions in France, Germany, and Italy: an analysis of treatment patterns, resource consumption, and costs.

PURPOSE: To describe treatment patterns among patients with central or branch retinal vein occlusion (CRVO or BRVO) in France, Germany, and Italy, and to estimate retinal vein occlusion (RVO)-related direct medical costs. METHODS: We used a retrospective chart review to determine 18-month RVO-related resource utilization and calculate 12-month health care costs. Country-specific unit costs (€) were assigned to each resource from the perspective of the health care payer. Costs for France and Germany were based on 2005, and for Italy on 2007 values. RESULTS: Data from a total of 109 BRVO and 119 patients with CRVO were used in the analysis. Laser therapy was the most commonly used intervention in Germany, for both CRVO and patients with BRVO (95%-98% of treatments), while patients in France with either condition had triamcinolone injections most often (63%-67% of treatments). Injections were also administered frequently in Italy and were the most common treatment for CRVO (50%), whereas patients with BRVO used laser therapy most often (41%). Inpatient treatment was most common in Germany (42% of CRVO and 34% of patients with BRVO), and did not occur at all in Italy except for day admissions. Total costs were higher for patients with CRVO in all countries. Most costs in Italy and France were attributable to outpatient treatment. In Germany, hospitalization made up the largest proportion of costs (80%), although more patients used outpatient services. CONCLUSIONS: Approaches to treating BRVO and CRVO vary across European countries. Development of agreed-upon guidelines would support consistency in patient care and reimbursement policy.

3-T Diffusion tensor imaging of the optic nerve in subjects with glaucoma: correlation with GDx-VCC, HRT-III and Stratus optical coherence tomography findings.

OBJECTIVES: To correlate diffusion-tensor imaging (DTI) of the optic nerve with morphological indices obtained by scanning laser polarimetry (GDx-VCC); confocal scanning laser ophthalmoscopy (Heidelberg III retinal tomograph; HRT-III) and optical coherence tomography (Stratus OCT). METHODS: Thirty-six subjects (12 with no eye disease and 24 with perimetrically diagnosed glaucoma) were examined. One eye for each participant was studied with 3-Tesla DTI (with automatic generation of mean diffusivity (MD) and fractional anisotropy (FA) values); GDx-VCC, HRT-III and OCT. Single and multiple regression analyses of all variables studied were performed. RESULTS: MD displayed the strongest correlation with linear cup/disc ratio (LCDR) from HTR-III (r=0.662), retinal nerve fibre layer (RNFL) thickness (avThickn) from OCT (r=-0.644), and nerve fibre index (NFI) from GDx (r=0.642); FA was strongly correlated with the LCDR (r=-0.499). In multiple regression analyses, MD correlated with LCDR (p=0.02) when all variables were considered; with avThickn (p<0.01) (analysis of all RNFL parameters); with NFI (p<0.01) (analysis of all GDx parameters); with avThickn (p<0.01) (analysis of OCT parameters); with LCDR (p=0.01) (analysis of HRT-III morphometric parameters) and with linear discriminant function (RB) (p=0.02) (analysis of HRT-III indices). As for FA, it correlated with avThickn (p=0.02) when we analysed the OCT parameters and with RB (p=0.01) (analysis of HRT-III indices). CONCLUSIONS: DTI parameters of the axonal architecture of the optic nerve show good correlation with morphological features of the optic nerve head and RNFL documented with GDx-VCC, HRT-III and OCT.

Differences between proximal versus distal intraorbital optic nerve diffusion tensor magnetic resonance imaging properties in glaucoma patients.

PURPOSE: To analyze in vivo the diffusion tensor magnetic resonance imaging (DT-MRI) properties of the intraorbital optic nerve at two different levels: Proximal to the optic nerve head (ONH) and distal to the ONH at the level of the orbital apex in glaucoma patients. METHODS: Twenty-four patients with primary open-angle glaucoma were examined. The categorization into early and severe glaucoma was performed by Hodapp's classification. Fifteen healthy individuals served as controls. DT-MRI was performed with a 3T-MR unit. RESULTS: At early stage mean diffusivity (MD) values were higher at the proximal site with respect to the distal site. On the contrary, a decrease in fractional anisotropy (FA) was observed only relative to patient stage, independent of optic nerve site. Moreover, at early disease stage an increase in overall diffusivities, was evident at the proximal site, whereas at the distal site a decrease of the largest diffusivity and an increase in both the intermediate and smallest diffusivities were observed. FA and MD measured at the proximal site, had, respectively, the highest sensitivity and specificity in discriminating between healthy and glaucomatous eyes. CONCLUSIONS: Our study represents the first attempt to evaluate in vivo fiber integrity changes along the optic nerve with DT-MRI. Optic nerve degeneration appears to be a process that affects differently the proximal and the distal segments of the optic nerve. The complementary high sensitivity of FA with the high specificity of MD at the proximal site may provide reliable indexes for the identification of glaucomatous patients at early stages.

Autologous conjunctival epithelium transplantation and scleral patch graft for postlensectomy wound leakage in Marfan syndrome.

PURPOSE: We report a case of woman with Marfan syndrome and longstanding postlensectomy scleral wound dehiscence. METHODS: A 34-year-old woman with Marfan syndrome who underwent lensectomy 20 years ago had conjunctival leakage with chronic hypotony and conjunctival cystic degeneration secondary to scleral wound dehiscence. Presentation, clinical evaluation, and particular treatment with autologous cultivated conjunctival epithelium transplantation and scleral patch graft are described. RESULTS: A 6-month follow-up confirmed complete epithelization of the ocular surface and absence of leaking from the wound with normal intraocular pressure. CONCLUSIONS: Transplantation of autologous cultivated conjunctival epithelium appears to be a valid strategy in the treatment of ocular disease requiring extensive excision of the conjunctiva.

Persistent epithelial defect after penetrating keratoplasty caused by adenoviral infectious keratitis.

A causal role of herpes simplex infection in persistent epithelial defect following penetrating keratoplasty (PKP) has been documented in the past. Instead, not much information is available on the role of adenovirus infection in delayed epithelization following PKP. Here, we describe a case of persistent epithelial defect due to adenoviral infection keratitis confirmed by PCR analysis. Adenovirus keratitis can be an unusual cause of delayed epithelization after PKP.

Modulation of Ku70/80, clusterin/ApoJ isoforms and Bax expression in indocyanine-green-mediated photo-oxidative cell damage.

PURPOSE: In order to characterize the biological effects and molecular mechanism underlying indocyanine-green (ICG)-mediated photo-oxidative cell damage, human cultured retinal pigmented epithelium (RPE) cells preloaded with ICG were exposed to 810-nm laser irradiation. Cell viability and death induction were examined, as well as the modulation of proteins involved in cell death and DNA repair. METHODS: ARPE-19 cells preloaded with 100 microM ICG were irradiated using continuous and micropulsed 810-nm laser for the dye photoactivation, and cell viability and apoptosis were evaluated. The expression and subcellular localization of Bax, Ku70, Ku80 and clusterin/ApoJ were analyzed by immunocytochemistry and Western blot. RESULTS: ICG photoactivation induced apoptosis in RPE cells. The micropulsed laser irradiation induced a higher percentage of cell killing as compared to continuous wave. Cell killing was inhibited by sodium azide, suggesting the involvement of reactive oxygen species in the laser-induced cell damage. Bax was strongly induced after 4 and up to 24 h of treatment. The nuclear proapoptotic isoform of clusterin/ApoJ was selectively upregulated after 24 h of treatment. The DNA repair machinery was upregulated after 4 and up to 24 h. CONCLUSION: These data elucidate some molecular mechanisms involved in cell death induced by ICG photosensitization. The increase and relocalization of Bax into the mitochondria and the upregulation and translocation of the proapoptotic isoform of clusterin/ApoJ in the nucleus demonstrated the involvement of these proteins in the photo-oxidative cell death pathway. These data point out new molecular targets and suggest potential applications in the therapy of the retinal diseases that could benefit by selective RPE treatment.

Association between lens opacities and mortality in the Priverno Eye Study.

BACKGROUND: Lens opacities are associated with a higher risk of death, although there are some discrepancies regarding the specific types of cataract representing risk. The purpose of the present study was to further investigate the relationships between different types of lens opacity and patient survival. METHODS: In 1987, 860 residents of Priverno, Italy, aged 45-69 years underwent an ophthalmologic examination. Based on patient histories and the findings of the slit-lamp examination, each of the 860 patients was classified according to the type of opacity (pure cortical, pure nuclear, pure posterior subcapsular, mixed, and surgical aphakia). The survivors of the original cohort were re-examined in 1994. Death and survival rates were computed by the Kaplan-Meier method. Associations between mortality and significant factors were included in a stepwise Cox proportional-hazards regression model. RESULTS: Forty-four members of the original cohort had died during the 7-year follow-up. Age-adjusted survival curves based on Kaplan-Meier estimates showed significantly lower survival in those whose baseline examinations had revealed pure nuclear opacity (log rank test: P=0.020) and aphakia (log rank test: P<0.001). When adjusted for other mortality risk factors (age, sex, diabetes, cardiovascular diseases), the hazard ratio was 4.32 for pure nuclear opacity (95% CI 1.13-16.4) and 18.3 for aphakia (95% CI 3.21-104.0). CONCLUSIONS: The analysis of the Priverno data seems to confirm an association between lower survival and cataracts, particularly those confined to the lens nucleus and those that had already prompted surgery.

Incidence of blindness and low vision in a sample population: the Priverno Eye Study, Italy.

PURPOSE: To study the incidence of blindness and low vision over a 7-year period. DESIGN: Population-based cohort study. PARTICIPANTS: The survivors of the original cohort of 860 persons from Priverno, Italy, aged 45 to 69 years, were reexamined. Of the 760 eligible survivors, 619 (81.4%) had a 7-year follow-up visit. METHODS: Baseline and follow-up examinations included the collection of anamnestic and ophthalmologic data by the same observers using the same methods and classification criteria to minimize sources of variability. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) measured at 4 m by standardized logarithmic chart was expressed as the logarithm of the minimum angle of resolution (logMAR). World Health Organization definitions of blindness and low vision were adopted (respectively, VA > 1.3 logMar and VA > 0.6 to 1.3 logMar in the better eye or in either eye). Participants at risk for visual impairment were those without blindness or low vision in one or both eyes at baseline; participants at risk for one-eye visual impairment were those without blindness or low vision in both eyes at baseline. RESULTS: A total of 33 participants were defined as incident cases of visual impairment. The overall incidence figures for blindness, low vision, one-eye blindness, and one-eye low vision were respectively 0.2% (95% confidence interval [CI], 0.0-0.9), 1.3% (95% CI, 0.7-2.6), 1.2% (95% CI, 0.6-2.4), and 2.9% (95% CI, 1.8-4.6). CONCLUSIONS: This study provides population-based estimates of the incidence of visual impairment in an adult, free-living European population. With respect to the younger participants, older subjects at baseline were at higher risk for incident visual impairment, the main causes of which were cataract, myopia, and diabetic retinopathy. The incidence of visual impairment in the subgroup aged 55 to 64 years at baseline was significantly higher than that found in Beaver Dam 5-year study and similar to that found in Beaver Dam 10-year Study, when the same definitions were adopted. This difference may be partially explained by social and cultural habits of the female samples, but many other factors may play a role.