Maurizio G. Uva

Standard-Fluence versus Low-Fluence Photodynamic Therapy in Chronic Central Serous Chorioretinopathy: A Nonrandomized Clinical Trial

PURPOSE To evaluate the efficacy of low-fluence compared with standard-fluence rate photodynamic therapy (PDT) for treating chronic central serous chorioretinopathy. DESIGN Prospective, multicenter, investigator-masked, nonrandomized clinical trial. METHODS Forty-two eyes (42 patients) with chronic central serous chorioretinopathy were enrolled; 19 eyes received indocyanine green angiography-guided standard-fluence PDT (50 J/cm(2)) and 23 eyes received indocyanine green angiography-guided low-fluence PDT (25 J/cm(2)). Primary outcome measures were the changes in mean logarithm of the minimal angle of resolution best-corrected visual acuity and the rate of eyes with complete subretinal fluid reabsorption. Secondary outcomes were the changes in central foveal thickness and choroidal perfusion. RESULTS Mean logarithm of the minimal angle of resolution best-corrected visual acuity improved significantly at all time points (P < .01), in the standard-fluence group from 0.43 to 0.24 at 12 months and in the low-fluence-group from 0.46 to 0.16, without significant difference between the 2 groups. At 12 months, a complete subretinal fluid reabsorption was seen in 15 standard-fluence-treated and 21 low-fluence-treated eyes (79% vs 91%; P = .5). In 1 standard-fluence eye, choroidal neovascularization developed at 3 months, and this eye received further PDT; in the other eyes, at 12 months, a moderate-significant choriocapillaris nonperfusion was seen in 8 standard-fluence-treated and 0 low-fluence-treated eyes (44% vs 0%; P = .002). CONCLUSIONS In most of the eyes, both standard-fluence PDT and low-fluence PDT resulted in complete subretinal fluid reabsorption with visual acuity improvement. Choroidal hypoperfusion related to PDT could be reduced by low-fluence PDT.

Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma

OBJECTIVE To evaluate the effect of Ginkgo biloba extract (GBE) on preexisting visual field damage in patients with normal tension glaucoma (NTG). DESIGN Prospective, randomized, placebo-controlled, double-masked cross-over trial. PARTICIPANTS Twenty-seven patients with bilateral visual field damage resulting from NTG. INTERVENTION Patients received 40 mg GBE, administered orally, three times daily for 4 weeks, followed by a wash-out period of 8 weeks, then 4 weeks of placebo treatment (identical capsules filled with 40 mg fructose). Other patients underwent the same regimen, but took the placebo first and the GBE last. Visual field tests, performed at baseline and at the end of each phase of the study, were evaluated for changes. MAIN OUTCOME MEASURES Change in visual field and any ocular or systemic complications. RESULTS After GBE treatment, a significant improvement in visual fields indices was recorded: mean deviation (MD) at baseline versus MD after GBE treatment, 11.40 +/- 3.27 dB versus 8.78 +/- 2.56 dB (t = 8.86, P = 0.0001, chi-square test); corrected pattern standard deviation (CPSD) at baseline versus CPSD after GBE treatment, 10.93 +/- 2.12 dB versus 8.13 +/- 2.12 dB (t = 9.89, P = 0.0001, chi-square test). No significant changes were found in intraocular pressure, blood pressure, or heart rate after placebo or GBE treatment. Any ocular and systemic side effects were recorded for the duration of the trial. CONCLUSIONS Ginkgo biloba extract administration appears to improve preexisting visual field damage in some patients with NTG.

Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Idiopathic Macular Hole: A Cross-sectional Prospective Study

PURPOSE To determine the choroidal thickness in the macular area in patients with idiopathic macular hole in one eye and an unaffected fellow eye and in healthy controls. DESIGN Cross-sectional, prospective study. METHODS Twenty-two patients with a full-thickness unilateral idiopathic macular hole and 22 age- and sex-matched controls were recruited. Enhanced depth imaging optical coherence tomography images were obtained by using spectral-domain optical coherence tomography. The choroidal thickness was measured in the subfoveal area and 1000 μm and 2000 μm away from the fovea in the nasal and temporal regions. The diameter of the macular hole and the axial length were determined. RESULTS Choroidal thickness was significantly different across the 3 groups at all locations (P < .001, analysis of variance). The choroid was significantly thinner in eyes with idiopathic macular hole and in unaffected fellow eyes than in the control group (P < .01, Tukey-Kramer test). The mean subfoveal choroidal thickness was 183.2 μm in the idiopathic macular hole group, 196.6 μm in the fellow-eye group, and 245.0 μm in the control group. A negative correlation between subfoveal choroidal thickness and axial length was found in all groups (macular hole, r = -0.53, P = .01; fellow eyes, r = -0.56, P < .01; controls, r = -0.52, P = .01); in control eyes, a negative correlation was found between choroidal thickness and age (r = -0.48, P = .02). CONCLUSIONS Choroidal thickness was reduced in eyes with idiopathic macular hole and also in fellow unaffected eyes. This may suggest a contributing role of the choroid in the pathogenesis of idiopathic macular hole.

Evaluation of central and peripheral corneal thickness with ultrasound biomicroscopy in normal and keratoconic eyes.

PURPOSE Our study was designed to calculate central and peripheral corneal thickness in patients affected with early stages of keratoconus and in normal subjects using ultrasound biomicroscopy (UBM). To obtain an objective and reliable assessment of the corneal thinning in affected eyes, we developed a keratoconus index (KI) by means of the UBM measurements. METHODS By means of the commercial version of the ultrasound biomicroscope (system model 840; Zeiss-Humphrey Instruments, San Leandro, CA, USA) using a 50-MHz probe, we studied 30 normal and affected eyes. In keratoconic eyes, we measured the thinnest corneal thickness (TCT) at the apex of the conus and at four peripheral sites at a distance of 2.5 mm from the central site (peripheral corneal thickness: PCT). The same procedure was performed in the normal eyes. To obtain an objective and reliable assessment of the corneal thinning, we calculated the ratio between the mean PCT and the mean TCT (Keratoconus Index: KI = PCT/TCT), in keratoconic eyes. In normal eyes, the KI was calculated on the basis of the ratio between the mean PCT and the mean central corneal thickness (CCT). RESULTS In keratoconic eyes, the mean corneal thickness at the thinnest part of the conus was significantly different from the CCT in normal patients (Students t test, p < 0.001). The peripheral measurements were not significantly different from keratoconic and normal eyes. The mean KI was 1.482 (SD, 0.095) in the keratoconic eyes, whereas it was 1.189 (SD, 0.086) in the normal subjects. The statistical analysis of the KI calculated on the basis of the UBM measurements showed that the KI values are significantly different from healthy subjects and from keratoconic patients (Students t test, p < 0.001). CONCLUSIONS UBM can be considered a useful tool in the study of keratoconus. We believe that calculation of the KI by means of UBM gives the possibility of obtaining an objective assessment of corneal thinning. Therefore this parameter can be useful in the staging and in the follow-up of these patients.

Pharmacological management of ocular hypertension: current approaches and future prospective

Elevated eye pressure is the main risk factor for glaucoma, and intraocular pressure rises when the balance between aqueous humor formation and outflow resistance is compromised. In a normal eye there is a precise tune of aqueous outflow under the fine control of ciliary body and trabecular meshwork. Current pharmacological therapies for lowering the intraocular pressure in glaucoma include increasing aqueous humor outflow and suppression of aqueous humor production. However, most of antiglaucoma drugs currently on the market do not target the trabecular meshwork that represents the site of the pathology. This review focuses on pharmacological management of ocular hypertension with a particular attention to the future pharmacotherapy scenario.

NINE-YEAR FOLLOW-UP OF TRABECULECTOMY WITH OR WITHOUT LOW-DOSAGE MITOMYCIN-C IN PRIMARY OPEN ANGLE GLAUCOMA

Aim: To evaluate the long-term efficacy and safety of trabeculectomy with or without low-dosage Mitomycin-C (MMC) in primary open-angle glaucoma (POAG). Methods: 114 patients affected by POAG, participating in a randomised clinical trial from 1995 to 1998, were re-examined and their chart reviewed. Patients had undergone in one eye a trabeculectomy with intraoperative application (2 min) of MMC (0.2 mg/ml) or balanced saline solution (BSS), and, if indicated, postoperative laser suture lysis, bleb needling and/or digital massage. Intraocular pressure (IOP), medical therapy, visual field, further glaucoma surgery, cataract surgery and complication rate (leakage, cataract progression, hypotony, blebitis, endophthalmitis) were evaluated. Results: 67 eyes had received MMC and 47 BSS. MMC-treated eyes had a lower mean IOP (13.33±3.35 vs 14.72±2.19 mm Hg, p = 0.014); in this group, an higher percentage of eyes had IOP⩽18 mm Hg (73.1% vs 51.1%, p = 0.027) and IOP⩽14 mm Hg (56.7% vs 31.9%, p = 0.015); a lower rate had further glaucoma surgery (9% vs 25.5%, p = 0.040), and visual-field damage progression (21.1% vs 48.6%, p = 0.009). No difference was seen in the complication rate: one MMC-treated eye developed blebitis. Conclusions: In POAG low-dose MMC with intensified postoperative management improved the outcome of the trabeculectomy with a low incidence of complications.

Low-fluence photodynamic therapy in longstanding chronic central serous chorioretinopathy with foveal and gravitational atrophy.

Purpose To describe anatomic and functional outcomes in two patients with long-standing severe chronic central serous chorioretinopathy (CSC) with foveal and gravitational atrophy treated with low-fluence photodynamic therapy (PDT). Methods Two patients with a history of over 10 years of chronic CSC and development of gravitational tracts, with best-corrected visual acuity <20/200, were treated with PDT guided by indocyanine green angiography (ICGA) with a fluence of 25 J/cm2 at an irradiance of 300 mW. Follow-up examinations 1 and 9 months after therapy included measurement of near and far best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography and ICGA, optical coherence tomography, and microperimetry. Results At 1 and 9 months after low-fluence PDT, complete resolution of subretinal, intraretinal, and under retinal pigment epithelium fluid was observed in both patients. Far and near visual acuity improved in both eyes. Improvement of sensitivity and fixation stability were demonstrated by microperimetry. No treatment-related side effects were seen. Conclusions ICGA-guided low-fluence PDT seems effective and safe for treating long-standing chronic CSC.

Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer’s disease

Amyloid deposits, constituted of amyloid beta (Aβ) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer’s, mild cognitive impairment and Parkinson’s disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of Aβ characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer’s disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-isoprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies.

Ultrasound-Biomicroscopic Evaluation of Filtering Blebs after Laser Suture Lysis Trabeculectomy

Sometimes in glaucomatous patients treated with trabeculectomy there is no correlation between bleb shape and intra-ocular pressure (IOP). In this study we evaluated the ultrasound biomicroscopy (UBM) features of filtering blebs after laser suture lysis (LSL) trabeculectomy in order to analyse whether its ultrasound-biomicroscopic image can predict the function (IOP). Methods: The Humphrey ultrasound biomicroscope, using a high-frequency (50-Mhz) probe, provides high-resolution images of filtering blebs. A total of 103 filtering blebs after LSL trabeculectomy were analysed by UBM. Taking into account the characteristics of internal reflectivity and scleral flap, we classified the blebs into three groups (good, fair, poor) that indicate the bleb function and correlated this UBM pattern with the IOP control (good, borderline, failure). Results: There was a statistically significant corelation between the UBM classification of function and the IOP control level. Both well-functioning and failed trabeculectomies could be identified by UBM. The UBM images of eyes with good IOP control are characterized by better visibility of the route under the scleral flap and a low reflectivity inside the bleb. Conclusions: In accordance with previous studies, we believe that UBM can be a useful method to study and explain the mechanisms of filtering structures and, together with IOP control, to evaluate the bleb function.

Intraocular pressure and central corneal thickness in premature and full-term newborns.

PURPOSE To evaluate the intraocular pressure (IOP) and central corneal thickness (CCT) in premature and full-term newborns. METHODS IOP and CCT were determined in 33 premature (mean [± SD] gestational age 31 ± 3 weeks, mean birth weight 1474 ± 354 g) and in 33 full-term white newborns (mean gestational age 39 ± 1 weeks, mean birth weight 2763 ± 574 g). The mean age after birth at measurement was respectively 3 ± 1 weeks and 1 ± 1 weeks. Infants with any ocular abnormalities, such as corneal and iris alterations, congenital cataract, retinopathy, glaucomatous corneal and optic disk changes (horizontal corneal diameter >10 mm Hg, C/D >0.4), or familial congenital glaucoma were excluded. IOP was determined with the use of only topical anesthesia with a Tono-Pen XL tonometer and a wire lid retractor, and then CCT was determined by means of a portable pachymeter. RESULTS Mean IOP was 18.9 ± 3.7 mm Hg (range, 13-25) in premature and 17 ± 2.6 mm Hg (range, 12-22) in full-term newborns (P = 0.018 after correction by age after birth). Mean CCT was 599 ± 36 μm (range, 524-720 μm) in premature infants and 576 ± 26 μm (range, 489-650 μm) in the full-term group (P < 0.001 after correction by age after birth). Multivariate analysis showed that IOP increased with increasing CCT (P = 0.025) and that CCT declined with increasing birth weight (P = 0.026). CONCLUSIONS In premature newborns, IOP measurements were slightly greater than in full-term newborns because of an increased CCT.