Abstract: PURPOSE: To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG). PATIENTS AND METHODS: In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 - IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight. RESULTS: Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it. CONCLUSIONS: Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.

Abstract: PURPOSE. To determine whether different coagulation-balance genetic polymorphisms might explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS. The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidences of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided in responder and non-responder basing on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms, i.e. factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS. Regression models documented that PDT-V non-responders were more frequent in patients with the hyper-fibrinolytic G185T mutation of factor XIII-A (OR = 0.28; 95% confidence interval [95% CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative for an over-representation of PDT-V responder among the combined carriers for thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% confidence interval [95% CI], 0.94-15.6; P = 0.07). All the other considered predictors did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS. These data provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in AMD patients affected by occult CNV.

Abstract: PURPOSE: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. METHODS: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. RESULTS: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P < 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. CONCLUSIONS: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.

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Abstract: AIM: To investigate whether dorzolamide modifies peripapillary retinal haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated with timolol. METHODS: In 40 JPOAG subjects, before and after dorzolamide coadministration with timolol, the following examinations were achieved: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), heart rate (HR), visual field and retinal flowmetry. RESULTS: Adjunctive therapy with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg, 95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95% CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not change. CONCLUSIONS: Dorzolamide, in association or in fixed combination with timolol, significantly improves retinal blood flow in JPOAG patients.

Abstract: PURPOSE: To verify the potential efficacy of intravitreal bevacizumab (IVB) injections for the treatment of retinal angiomatous proliferation (RAP). DESIGN: Retrospective interventional case series. METHODS: Four consecutive patients affected by RAP at different stages and refractory to photodynamic therapy (PDT). All patients underwent a complete ophthalmic examination including best-corrected visual acuity (BCVA), fluorescein and indocyanine green angiographies, and optical coherence tomography (OCT) at baseline, and after one, three, six, nine, and 12 months. All patients received IVB injections (1.25 mg/0.05 ml). RESULTS: The best functional response has been achieved in patients with RAP at stages 1 and 2; whereas in stage 3, a detectable recovery of visual acuity was not observed. This improvement was stable over the follow-up period with a concomitant reduction of macular thickness. CONCLUSIONS: The use of IVB in patients affected by RAP seems to exert morphologic benefits at all RAP stages that does not always correspond a functional improvement.

Abstract: OBJECTIVES: Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. As PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy. METHODS: Ninety Caucasian patients with neovascular AMD were subdivided in responder and nonresponder, on the basis of CNV responsiveness to PDT-V application. Six gene polymorphisms, that is factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in the entire cohort. RESULTS: Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [odds ratio (OR)=5.6, 95% confidence interval (CI) (1.2, 27.2), P=0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR=6.9, 95% CI (2.7, 18.1), P<0.001]. Conversely, PDT-V nonresponders were overrepresented in carriers for factor XIII-A 185T [OR=0.13, 95% CI (0.05, 0.36), P<0.001]. CONCLUSION: These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.

Abstract: PURPOSE: To investigate retinal blood flow by Heidelberg retina flowmeter in patients with active Graves' ophthalmopathy. MATERIALS AND METHODS: Thirty patients with active Graves' ophthalmopathy in euthyroid state and thirty normal controls were enrolled in this study. All subjects underwent heart rate, systolic and diastolic blood pressure detection, complete ophthalmological examination, Hertel's exophthalmometry, and retinal blood flow analysis by Heidelberg retina flowmeter. Patients additionally underwent automated threshold perimetry and extraocular muscle thickness measurement by A-scan ecography. RESULTS: A significant statistical difference was found in exophthalmometry (P<0.001), intraocular pressure (P<0.001) and retinal blood flow (P<0.05) between patients and controls. In patients, muscle enlargement was significantly correlated with retinal blood flow (r=0.49, P=0.005) and proptosis (r=0.37, P=0.04). A significant positive correlation (r=0.52, P=0.002) was also found between intraocular pressure and proptosis. CONCLUSIONS: Active Graves' ophthalmopathy patients present an increased retinal blood flow.

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Abstract: PURPOSE: To verify the short-term influence of an orally administered nonsteroidal anti-inflammatory drug on the intraocular pressure (IOP) of primary open-angle glaucoma patients in therapy with a topical prostaglandin analog. DESIGN: Randomized cross-over double-blind study. METHODS: Sixteen adults with primary open-angle glaucoma, receiving 0.005% latanoprost eyedrops once daily, were treated with a single dose of either 100 mg nimesulide or placebo. IOP was recorded at baseline and at 1, 2, 4, 8, 12, and 24 hours. RESULTS: After nimesulide administration, there was a decrease in IOP (with a fall at the second hour, P<.01) that remained significant 8 hours later (P<.05). At 12 and 24 hours, there were unremarkable IOP differences between the two regimens. CONCLUSIONS: In patients with primary open-angle glaucoma, single-dose nimesulide significantly enhances the latanoprost-induced IOP-lowering effects during the short plasma half-life of this non-steroidal anti-inflammatory drug.

Abstract: The aim of this randomized, prospective, masked clinical study has been to verify the influence of a non-steroidal anti-inflammatory drug ophthalmic solution on intraocular pressure reduction induced by 0.5% timolol and 0.005% latanoprost eyedrops in patients affected by primary open-angle glaucoma. Thirty-two glaucomatous patients, compensated with 0.5% timolol, were randomized into two study groups (A and B). Timolol was continued for the first 2 weeks in all subjects. On the 15th day, in both groups timolol was replaced by latanoprost, and this regimen lasted up to the end of the follow-up (8 weeks). At the beginning of the 2nd week of the study, group A additionally started a 5-week therapy with topical 0.1% diclofenac; during the same period, group B received placebo eyedrops with identical modalities. Intraocular pressure was recorded at 7-day intervals during the first 7 weeks and at the 10th week. Non-steroidal anti-inflammatory drug and placebo did not modify the effect of timolol on intraocular pressure. In both groups, latanoprost induced a significant decrease in intraocular pressure. Diclofenac-treated patients exhibited a marked fall in intraocular pressure (p<0.01), whereas in placebo-treated patients, this diminution was less noticeable (p<0.05). After diclofenac withdrawal, in group A intraocular pressure significantly increased (p<0.01), remaining approximately at the same level up to the end of the study. In group B, at the same checks no significant variations in intraocular pressure occurred. In primary open-angle glaucoma patients, diclofenac significantly enhances the hypotensive effect of latanoprost, without influence on timolol efficacy. Because non-steroidal anti-inflammatory drugs are widely employed in medical practice, supplementary ophthalmologic checks should be scheduled during the co-administration of these compounds and prostaglandin analogues.

Abstract: A 25-year-old white, HIV-positive, immuno-competent man was referred to us because of a progressive blurred vision in his right eye. Clinical characteristics were suggestive for an unilateral fungal endophthalmitis, and thereby fluconazole firstly, followed by conventional amphotericin B were intravenously administered, without any significant improvement. Thus, a pars plana vitrectomy was performed. Aspergillus versicolor was isolated from the cultures of the vitreous sample and intravenous liposomal amphotericin B was administered. An increase of visual acuity together with a reduction of vitreous inflammation occurred. This case of ours represents the first report describing an endogenous endophthalmitis induced by Aspergillus versicolor.

Abstract: Purpose To report the clinical association between macular coloboma (early-onset macular dystrophies/atrophic changes) and different phenotypes of retinitis pigmentosa (RP).Methods Three young-adult siblings, two males and one female, were retrospectively studied. These patients underwent two complete ophthalmologic examinations (27-month follow-up), including orthoptic evaluation, colour vision test, visual field, corneal topography, electronystagmography, fluorescein angiography, and electroretinography. Eye check, automated visual field test, and complete electroretinographic study were also conducted on other asymptomatic members of the same family.Results All symptomatic siblings were affected by manifest congenital nystagmus, poor visual acuity, and progressive visual field impairment in both eyes, bilaterally presenting macular coloboma associated with three different RP patterns: classic RP; mild dystrophy of the retinal pigment epithelium, associated with subnormal electroretinographic findings (subclinical form of RP); and sector RP. The ophthalmologic reports regarding their deceased father documented that he had suffered from the same alterations of ocular movements and visual performances diagnosing, in both eyes, extensive atrophic changes of the macular area completely surrounded by pigmented bone spicules (RP-type tapeto-retinal dystrophy). The other investigated relatives did not show any specific and/or significant ocular disorder.Conclusions In these three adult members of the same family, the concomitance between macular coloboma and different intrafamilial RP phenotypes is described. This association represents an autosomal dominant clinical entity, hitherto observed only in non familial sporadic cases.Eye (2004) 18, 421-428. doi:10.1038/sj.eye.6700689

Abstract: Gyrate atrophy of the choroid and retina is an autosomal recessive chorioretinal dystrophy which leads to a slowly progressive loss of vision. The primary defect is due to a deficiency of the enzyme ornithine delta-aminotransferase, which is responsible for markedly elevated levels of ornithine in plasma and other body fluids. Although several therapeutic regimens have been proposed, the reduction in ornithine accumulation obtained by reducing the intake of its precursor arginine (semisynthetic low-arginine diet) is the one most practised. In this clinical and molecular study we report a patient with hyperornithinaemia and gyrate atrophy of the choroid and retina who had been diagnosed when she was 3 years 9 months old. She also presented mild mental retardation, delayed language development and speech defects. The patient has recently been found to be homozygous for the new Gly91Arg amino acid substitution of the enzyme ornithine delta-aminotransferase. This mutation lies in a region of the mature protein that is considered crucial for the mitochondrial targeting activity. In this patient, a 28-year treatment with a completely natural low-protein diet (0.8 g/kg per day of natural protein) has been able to significantly reduce ornithine plasma levels, and to greatly delay the natural progression of the chorioretinal changes. This study suggests that, in the long-term treatment of gyrate atrophy, the efficacy in slowing the progression of chorioretinal changes and the palatability of a completely natural low-protein diet make this treatment a potentially viable alternative in patients refusing the semisynthetic diet.

Abstract: PURPOSE: To verify the prevalence of Val34Leu polymorphism in factor XIII A-chain gene (FXIII Val34Leu) in patients with spontaneous subconjunctival hemorrhage (SCH). DESIGN: Nonrandomized case-control study. METHODS: One hundred seven white patients suffering from one or more episodes of idiopathic SCH and 107 healthy subjects were matched for age and gender, and genotyped for FXIII Val34Leu. Anamnestic, ophthalmologic, cardiovascular, and serologic examinations were performed. RESULTS: Frequency of FXIII mutated allele (Leu34) was significantly higher in SCH patients than in controls. Computing together heterozygotes (Val/Leu) and homozygotes (Leu/Leu), genotype distribution was statistically different. In a conditional logistic regression model, the comparison of the three separated genotypes, performed among 25 patients with recurrent idiopathic SCHs and controls, gave significant differences for both Val/Leu and Leu/Leu variables. CONCLUSION: Both homozygosity and heterozygosity for FXIII Val34Leu predispose to idiopathic SCH, emphasizing the role of Leu34 allele as inherited risk factor for spontaneous, especially recurrent, SCHs.

Abstract: SSRIs are the most commonly prescribed antidepressant drugs, in part because of their favourable safety profile compared with older antidepressants. However, the widespread use of SSRIs leads to an increased occurrence of rare adverse effects. This review, based on data from published experimental research, clinical studies and case reports, describes the role of serotonin in the control of intraocular pressure (IOP) and the evidence for IOP modifications in patients receiving SSRIs. In a small percentage of patients with depression, the cause of SSRI withdrawal has been the occurrence of ill-defined visual disturbances. It can be speculated that in some of these patients, the iatrogenic ocular alterations could have been due to changes in IOP. There have also been a limited number of case reports of acute attacks of glaucoma occurring during treatment with SSRIs. Although causality is not exactly specified, the relationship between SSRIs and this ocular adverse event is strongly implied. Nevertheless, in a small clinical study assessing the effect of a single dose of fluoxetine on IOP, the drug was shown to increase this parameter, although the effect was asymptomatic. The clinical signs of unexpected adverse drug effects are often disregarded, with the exception of those characterised by serious symptoms (such as acute angle-closure glaucoma in the case of IOP modifications). Also, the distribution of iridocorneal angle configurations in the general population implies that an adverse effect on IOP will be pauci- or asymptomatic in most patients (intermittent, sub-acute or progressive angle-closure glaucoma). As a result, it is likely that the incidence of SSRI-related IOP modifications is underestimated. Until the involvement of SSRIs in IOP modifications is better understood, ophthalmological consultations should be considered before starting and during treatment with any SSRI in patients with glaucomatous risk factors, especially those who are elderly.

Abstract: BACKGROUND/OBJECTIVE: Clear cell renal cell carcinoma (CCRCC) is a malignant neoplasm frequently associated with an increase in circulating immune complexes (CIC). Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a disease involving the chorioretinal structures of the eye, and it is commonly observed in association with several immunogenic disorders. We report here the clinical association between humoral immunologic modifications during tumoral diseases (long-standing CIC increase) and chorioretinal changes resembling atypical APMPPE. CASE REPORT: A 52-year-old white male affected by metastatic CCRCC is described. Histopathologic review of his surgically removed organs (kidney and lung), periodical laboratory immunologic tests and ophthalmologic examinations, including fluorescein and indocyanine green angiographies, were performed. RESULTS: The patient underwent total left nephrectomy (May 1997) and total left pneumonectomy (March 2001) for the presence of stage III CCRCC and CCRCC lung metastasis, respectively. On both occasions, postoperative immunotherapy was started. From June 1997 to February 2003, laboratory analyses demonstrated the presence of marked CIC peaks. During the follow-up period, an atypical APMPPE pattern, complicated by asynchronous choroidal neovascularization, occurred in both eyes. CONCLUSIONS: Long-standing tumorous disease, through a pathogenic mechanism triggered by CIC spreading, can be responsible, over time, for a progressive choroidal occlusive microangiopathy (atypical APMPPE pattern), associated with a high risk of poor visual outcome. Therefore, bilateral APMPPE could be related to a systemic disease able to increase CIC levels.

Abstract: OBJECTIVE: The aim of this study was to verify the acute effects of alpha-adrenoreceptor agonist eyedrop administration on visual field parameters and ocular perfusion pressure (OPP) in patients affected by primary open-angle glaucoma. METHODS: A prospective, randomized double-blind study was carried out. Sixty-four glaucomatous subjects were enrolled in the clinical trial and subsequently separated into four study groups, of 16 patients each, to compare the systemic and ocular effects of placebo, clonidine 0.125%, apraclonidine 1.0% and brimonidine 0.2%. RESULTS: No significant variations in the ocular or systemic parameters were observed after placebo administration. All the alpha-adrenoreceptor agonist compounds induced a significant reduction of the intraocular pressure. Clonidine induced significant modifications of mean blood pressure, OPP and visual field indices. The acute administration of apraclonidine did not affect both mean blood pressure and OPP, but a worsening of the visual field was nevertheless recorded. The analyzed parameters did not significantly vary after brimonidine instillation. CONCLUSIONS: The present findings demonstrate that the lack of effects on the blood flow and the absence of vasomotor activity at the level of the posterior pole exhibited by brimonidine is related to its alpha-2 selectivity, as appears by comparing this compound with the other alpha-agonists available for the management of glaucoma.

Abstract: PURPOSE: To report a clinical association between congenital adrenal hyperplasia and keratoconus. DESIGN: Observational case report. METHODS: Two 25-year-old dizygotic female twins were retrospectively studied. Clinical history, hormonal serologic profile, complete ophthalmologic examination, and Holladay Diagnostic Summary variables were evaluated. In the course of a 15-month follow-up period, a progression of the corneal disease was observed. RESULTS: In both twins a diagnosis of nonclassical congenital adrenal hyperplasia, due to 21-hydroxylase deficiency, was established when they were 21 years old. In one subject, the computed corneal topographic analyses diagnosed an asymmetric keratoconus in both eyes. A progressive form of fruste central keratoconus was also documented in her sister. CONCLUSIONS: Congenital adrenal hyperplasia may be associated with keratoconus. An abnormal steroidogenic pathway, affecting the normal development of the cornea, could induce stromal abnormalities that lead to corneal ectasia.

Abstract: Glaucoma is a pathological condition whose most important risk factor is increased intraocular pressure (IOP). The medical treatment of glaucoma essentially consists of compounds that are able to decrease the IOP. The compounds discussed in this review act in a different way, beta-blockers mainly inhibit the production of aqueous humor, whereas latanoprost decreases the resistance in the outflow channels. beta-Blockers are compounds with a well-known efficacy and safety profile and they are fairly inexpensive. Their systemic and local side effects are mainly cardiovascular and pulmonary adverse events, dry eye and keratopathy. Latanoprost, which has recently been introduced into the market, has been shown to be equally as effective, or better in lowering IOP in patients than timolol, although it is more expensive. Systemic reported side effects are anecdotal; local hyperaemia, keratopathy, hypertrichosis, increased pigmentation of eyelashes and iris, uveitis and cystoid macular oedema have been reported. A comparison of costs reveals that a 1-year therapy with timolol ophthalmic solution starts from 11.00 Euros and can reach 146.00 Euros for the most expensive preservative-free 1-day dispenser packages (approximately 13.5 times higher). For latanoprost once-daily administration, the cost for 1 years therapy is 98.55 Euros, approximately six times higher than generic or brand 0.5% timolol applied twice-daily. What are the factors influencing a change in therapy from beta-blockers to latanoprost? The only good reason is represented by a further deterioration in the visual field. This may occur, despite a significant reduction in IOP, because the reached IOP is not sufficient enough to avoid further deterioration because the patient's work or social activities do not allow a correct daily dosage of the compound (bad compliance); or as a result of treatment suspension, because of the development of systemic and/or local side effects. Changes in therapy must always be related to a failing control of the disease, as any therapeutic modification leading to an increase in the number of visits and additional examinations, consequently enhances the costs.

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Abstract: AIMS: Retinal venous tortuosity (RVT) is a common finding in patients affected by different forms of chronic anaemia. The aims of this study were to quantify RVT in anaemic patients with beta-thalassaemia major and to verify whether it is related to some of the following parameters: patient's age, ferritin plasma level, and Desferrioxamine (DFX) daily dosage. METHODS: A retrospective study was carried out. In total, 36 consecutive thalassaemic patients, treated with polytransfusion regimen and DFX, were age- and sex-matched with a control group of 36 normal subjects. All subjects bilaterally underwent red-free fundus photography, centred on the optic disc. The four main retinal veins were measured with a computer-assisted method. RESULTS: Mean venous length in the thalassaemic group was significantly greater than that observed in the control group (P <0.001). In thalassaemic patients, no significant correlations between retinal venous length and, respectively, plasma ferritin level and DFX daily dosage were documented. Statistical analysis demonstrated a very significant association between patient's age and increased RVT only in thalassaemic patients (P <0.001). CONCLUSIONS: Our findings demonstrate that patients with beta-thalassaemia major have increased RVT, as compared to normal subjects. In this selected anaemic population, patient's age, closely related to anaemia duration, is the only variable responsible for the RVT increment. This clinical sign indicates a long-standing duration of anaemia.

Abstract: PURPOSE: To assess the efficacy and side effects of 0.005% latanoprost once daily during 3 years of treatment in glaucomatous patients in whom intraocular pressure (IOP) was not adequately controlled by beta-blockers twice daily.METHODS: An unmasked prospective study was performed on 76 glaucomatous patients (145 eyes) treated with 0.005% latanoprost at bedtime, after a 21-day wash-out period from beta-blockers. IOP measurement and visual field examination were recorded over the follow-up period.RESULTS:Latanoprost significantly reduced IOP from 26.5+/-6.6 mmHg (mean +/- SD) to 17.4+/-2.7 mmHg after 36 months of treatment in 48 patients (63.1%), who completed the trial. Twenty-eight patients (36.8%) discontinued the therapy. In 12 patients (15.8%) the treatment did not obtain a satisfactory target IOP. In two subjects (2.6%), despite the IOP reduction, visual field damage progressed. The remaining 10 patients (13.1%) discontinued the treatment because of the following side effects: microfollicular conjunctivitis (seven cases); severe oedema of conjunctiva and eyelids (one case); corneal punctate erosion (one case); cystoid macular oedema (one case). No flare or pigmentary changes of iris and eyelash were observed.CONCLUSION: Latanoprost 0.005% once daily significantly reduces IOP in the majority of glaucomatous patients uncontrolled by beta-blockers. The reduction of IOP was statistically significant during 3 years of follow-up, confirming the clinical efficacy of this compound. The ocular side effects requiring cessation of therapy were mainly allergic reactions. The most severe adverse effects were one case of corneal punctate erosion and one case of cystoid macular oedema in a pseudophakic patient.

Abstract: PURPOSE: To investigate the cause of recurrent central retinal vein occlusion in a 26-year-old white woman. METHODS: Case report. Complete blood analyses were done, including HLA tissue typing, immunoserologic and coagulation tests, with cardiovascular and capillaroscopy investigations. Factor V:R506Q and prothrombin 20210 GIA mutations were checked by polymerase chain reaction and restriction enzyme analysis. RESULTS: DNA analysis showed the patient to be heterozygous for factor V:R506Q mutation. During a follow-up of 18-months, after starting anticoagulant therapy, the patient had not suffered from any other ocular or systemic occlusive vascular accident. CONCLUSIONS: The R506Q factor V gene mutation may be associated with recurrent central retinal vein occlusions. Genetic investigation should be promptly recommended in thrombotic patients to establish a specific preventive treatment.

Abstract: PURPOSE: To report a mesectodermal leiomyoma of the posterior choroid. DESIGN: Observational case report. METHODS: A 23-year-old man was referred to us because of a progressive blurred vision in his left eye. Ophthalmologic examination revealed the presence of a 12 x 10 x 7.2-mm amelanotic choroidal mass in his left posterior pole. Fluorescein angiography, A-scan ultrasonography, and B-scan echography findings were suggestive for a diagnosis of choroidal amelanotic melanoma. These clinical features prompted us to enucleate the left eye. RESULTS: Histopathological and immunohistochemistry examinations established a definitive diagnosis of mesectodermal leiomyoma of the posterior choroid. CONCLUSION: This case represents the first report describing the occurrence of an intraocular mesectodermal leiomyoma that may exclusively involve the posterior choroid.

Abstract: PURPOSE: To describe the concomitant occurrence of systemic cortico-steroid treatment and the development of bilateral central serous chorioretinopathy (CSC), which promptly regressed after the reduction of the drug dosage, up to its scheduled withdrawal. METHODS: Case report. RESULTS: A 46-year-old white male, with a history of monolateral CSC, had a non-Hodgkin lymphoma on his right cheek. Soon after surgical excision of the tumoral lesion, he received a standard post-operative regimen of decreasing intramuscular betamethasone for 25 days, followed by 10 day's withdrawal, then cycles of intravenous cyclophosphamide and vincristine, followed by 7-day oral prednisone, repeated monthly for three months. Fluorescein angiographies at the end of the first oral cortico-steroid cycle and before starting the second, documented the occurrence of bilateral CSC and its regression, which were chronologically related respectively to the cortico-steroid administration and withdrawal. CONCLUSIONS: This case further demonstrates that systemic cortico-steroids can be responsible for the occurrence of CSC. The patient's history should always be checked for any previous CSC episodes. In these subjects, periodical ophthalmoscopic examination is essential to discover early or asymptomatic steroid-related CSC patterns, to prevent complications of the disease.

Abstract: PURPOSE: To report on the occurrence of frequent episodes of spontaneous subconjunctival hemorrhage (SCH) in patients with the Leu 34 allele of the coagulation factor XIII (FXIII), known to be associated with high hemorrhagic risk. DESIGN: Observational case series. METHODS: Five young adults who had suffered from recurrent idiopathic SCH not associated with any recognized ocular and systemic hemorrhagic risk factor were investigated. Accurate anamnestic, ophthalmologic, hematologic, and serologic examinations were performed, together with blood pressure measurements, electrocardiogram (ECG), and 24-hour Holter ECG recordings. FXIII Val34Leu polymorphism was studied by DNA chain polymerase reaction. RESULTS: DNA analyses showed that the hemorrhagic mutated Leu34 allele was present in four of our selected patients: two mutated homozygotes (Leu/Leu) and two heterozygotes (Val/Leu). In the last subject this polymorphism was not detected. All the other clinical evaluations did not disclose any significant abnormality. CONCLUSIONS: The FXIII Val34Leu mutation may be associated with an increased risk for spontaneous episodes of SCH.

Abstract: PURPOSE: To report a case of monolateral preretinal fibrovascularproliferations in a young adult woman, who had suffered from incontinentia pigmenti (IP) during her first month of life. METHODS: Case report. RESULTS: Circumscribed preretinal fibrovascular proliferations, adjacent to a mid-peripheral area of snail track degeneration, were occasionally diagnosed in the left eye of an asymptomatic 18-year-old white female. Careful ocular examination did not reveal any cause of the monolateral vascular abnormalities observed in the posterior segment. A detailed medical history brought to light that the patient has suffered infantile IP, like four other females in her family. The patient did not present any evident malformation of teeth, nails, skeleton or hair. A cytogenetic linkage study documented a chromosomal aberration in the Xq28 band, which confirmed the diagnosis of familial IP (type 2). The fluorescein angiography findings clearly illustrated the minimal retinal involvement in the course of IP. CONCLUSIONS: This case shows that a wide range of etiologies must be considered in patients presenting monolateral preretinal fibrovascular proliferations. To correctly manage these uncommon, inherited or acquired, retinal diseases it is better to do a mid-term follow-up, rather than operate immediately, and this enabled us to observe the natural course of the lesion, while awaiting a definitive diagnosis.

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Abstract: BACKGROUND: Several inherited conditions have been associated with an increased or decreased incidence of retinal vein occlusion (RVO). The A allele in the 20210 G/A prothrombin gene has been found to be associated with systemic venous thrombosis. The aim of this study has been to verify the prevalence of this mutation in patients affected by central RVO (CRVO) or branch RVO (BRVO). METHODS: A retrospective study was carried out on 100 consecutive patients suffering from RVO, more than 50 years old, unaffected by systemic diseases known to be associated with markedly increased RVO occurrence. We determined the frequency of this mutation by performing mutagenised amplification of exon 14 followed by restriction analysis of the amplified DNA fragment. RESULTS: The overall frequency of prothrombin 20210A allele in RVO patients was 6.0%. All heterozygous patients had suffered from CRVO. In this study subgroup, the frequency of the 20210 G/A prothrombin heterozygosis was 12.0%. The difference in the frequency of this the genetic variant between the CRVO and BRVO groups was statistically significant. None of the conventional RVO risk factors were statistically related to the occurrence of the disease in either the CRVO or the BRVO subgroup. CONCLUSION: The prevalence of the prothrombin 20210A mutation observed in CRVO patients is significantly higher than in the normal Italian population. Moreover, the prevalence is significantly greater in CRVO than in BRVO patients. These results raise the possibility that the prothrombin 20210A variant may be considered as a risk factor for CRVO.

Abstract: PURPOSE: To examine the relation between perfusion of the optic nerve head and visual field defects in glaucomatous patients. METHODS: A study was performed on 94 patients affected with primary open-angle glaucoma. The optic nerve head blood flow was measured by means of a scanning laser Doppler flowmeter (Heidelberg Retina Flowmeter). Blood volume, flow and velocity were analysed in two areas of the rim and in one area of the lamina cribrosa. The visual field was tested with the 30-2 full threshold white-on-white program and mean deviation (MD) and corrected pattern standard deviation (CPSD) were considered as parameters of visual field defects. RESULTS: The interindividual analysis showed that the vascular parameters of the neuroretinal rim circulation were not significantly correlated with visual field parameters. The blood volume, flow and velocity of lamina cribrosa correlated significantly with both MD (R=0.519, R=0.549 and R=0.531, respectively; P<0.001) and CPSD (R=-0.496, R=-0.363 and R=-0.363, respectively; P<0.001). The intraindividual correlations (right-left differences of parameters) showed that the side differences of MD and CPSD correlated significantly with the side differences of blood volume (R=0.511 and R=-0.477, respectively), flow (R=0.554 and R=-0.390, respectively) and velocity (R=0.541 and R=-0.372, respectively) in lamina cribrosa. CONCLUSION: These findings suggest that in glaucoma patients the perfusion parameters of lamina cribrosa are significantly correlated with visual field defects.

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Abstract: BACKGROUND: This study evaluated the conjunctival effects of latanoprost and timolol, both of which contain benzalkonium chloride, in patients with primary open-angle glaucoma (POAG), with and without a history of allergic conjunctivitis (AC). METHODS: Two groups of 25 patients with and without a positive history for AC were studied. After a 21-day wash-out period patients were randomized to 14 days treatment with latanoprost or with timolol, in a cross-over fashion. The following parameters were evaluated on days 0 and 14: number of white blood cells, ferning test, conjunctival impression cytology, subjective symptoms, and objective ocular changes. RESULTS: Latanoprost caused: (a) an increase in eosinophils in both groups and reduction in lymphocytes only in the group with a history of AC; (b) alterations in ferning test and impression cytology only in AC patients; and (c) development of subjective symptoms and objective signs only in non-AC glaucomatous subjects. Timolol therapy was responsible only for the occurrence of subjective symptoms and objective signs in non-AC patients. CONCLUSION: Latanoprost treatment induces ocular surface changes which are more evident in POAG patients who are also affected by AC. These findings are probably related to the very high latanoprost concentration of benzalkonium chloride and to its bedtime administration, which further amplifies the toxicity.

Abstract: The effects of fluoxetine, which is a selective inhibitor of serotonin reuptake (SSRI) have been studied on the intraocular pressure (IOP) in the rabbit. IOP was measured using a Perkins tonometer. Intravenous administration of fluoxetine (6.0 mg kg-1) significantly increased IOP by 7.2 +/- 1.3 mmHg (P < 0.001). Fluoxetine administration also reduced the amount of urine excreted during the 24 hr, and increased the urine concentration of 5-hydroxyindole acetic acid (5-HIAA). Topical preadministration of ketanserin prevented a rise in IOP, without there being any effects on the other parameters examined. These findings indicate that intravenous administration of fluoxetine is able to raise IOP, through increased plasma levels of serotonin, which is confirmed by elevated 5-HIAA urine excretion and reduction in diuresis. Ketanserin, a specific 5-HT2A antagonist, counteracts the IOP increase brought about by fluoxetine, thus emphasizing the role of serotonin in the regulation of IOP and stressing the importance of including ophthalmological examination in the protocol of depressed patients undergoing SSRI therapy.

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Abstract: The authors describe a case of bilateral pattern dystrophy of the retinal pigment epithelium in a man with Crohn's disease. The patient was examined every 6 months over a follow-up of 30 months. The right eye presented a macroreticular dystrophy while in the left eye a butterfly pattern dystrophy was diagnosed. During the follow-up period the retinal lesion changed; in the right eye the lesion increased in size, while in the left eye the morphology of the lesion passed from the butterfly to Sjögren's type. This report adds a new ocular manifestation of Crohn's disease, emphasizing the importance of the ophthalmological follow-up in the recognition of posterior segment complications associated with this inflammatory bowel disease.

Abstract: The effects of the type 1 angiotensin II receptor antagonist Losartan potassium on intraocular pressure (IOP) were studied. Four groups of subjects were analysed: group A, ten controls; group B, ten patients with essential arterial hypertension and with IOP within the normal range; group C, ten patients with primary open angle glaucoma (POAG), but without essential arterial hypertension; group D, ten patients with arterial hypertension and POAG. The study design was held in a randomized crossover double-blind fashion. Systolic and diastolic arterial pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1 hr intervals up to 6 hr, following the oral administration of 50 mg of Losartan potassium and/or placebo. The alternative treatment was given a week later. Drug administration significantly reduced IOP in all subjects. No variation in heart rate and pupil diameter was observed during the follow-up period. Blood pressure dropped only in arterial hypertensive patients (groups B and D). Total outflow facility increased significantly in all groups. Placebo did not induce any variation in all groups. These findings demonstrate that the mechanism by which Losartan potassium reduces intraocular pressure is not mediated by a decrease in blood pressure, but rather it is more specific, confirming the role of the renin-angiotensin system also in the regulation of intraocular pressure in man.

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Abstract: Using eyelid sutures, we induced axial elongation in 20 15-day-old rabbits. When the eyelid sutures were opened, the eyes revealed a slight increase in their axial length. This evident axial elongation continued to evolve despite restitution of functional integrity to the previously sutured eyes. We suspect that because the lid sutures altered visual input and inhibited the retina from maintaining control of ocular growth, the retina instigated excessive eye growth, resulting in the initial consequent axial elongation that was evident on removal of the sutures. Additionally, poor quality of the retinal image, probably resulting from the noncorrected myopic ametropia caused by the lid sutures, could be the cause of the continued axial length increase observed after the lid sutures were removed.

Abstract: The aim of this study was to verify the in vitro influence of various dilutions of a viscoelastic substance containing 2% hydroxy-propyl-methylcellulose (HPMC) on the viability of some microbial strains representative of the normal flora of the external eye. Pure reference strain cultures of Candida albicans, Pseudomonas aeruginosa, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis and a fresh clinical isolate of Proteus mirabilis were selected for this study. Serial twofold dilutions of 2% HPMC, prepared so as to obtain a final concentration ranging from 50 to 0.78% of the product in sterile saline solution (0.85% NaCl), were taken out with a pipette that delivered 1.0 ml per tube. One hundred microliters of the abovementioned microbial inocula, used for the evaluation of the positive control of the test organism, were dispensed into each tube. After 24 h of incubation, 100 microl of samples were taken from each tube and plated into the specific medium for the growth of the test organism. After 24-48 h of incubation, these agar plates were examined and the colony-forming-unit count of each test organism was compared to the corresponding total colony count, acting as a positive control, in order to determine the quantitative variation of the test organism grown in the presence of the viscoelastic compounds. C. albicans and P. aeruginosa showed a statistically significant increase in growth with HPMC dilutions varying from 1:2 to 1:16. P. acnes and P. mirabilis growth was significantly reduced by all dilutions except for the 1:128 one. S. epidermidis growth was also significantly reduced in the presence of HPMC dilutions varying from 1:2 to 1:64. S. aureus growth was not significantly influenced. The viability of P. aeruginosa in HPMC dilutions needs to be carefully considered because of the ability of this organism to induce endophthalmitis, and the possibility that during cataract surgery, a small amount of HPMC may be left in the eye, trapped behind the intraocular lens optic.

Abstract: The aim of this study has been to assess the clinical presentation and biochemical profile of lipoid proteinosis within a defined pedigree. Glycoprotein analysis was compared to normal values in an attempt to define a biochemical phenotype. Six affected family members were identified with variable degrees of disease expression. The most likely mode of inheritance is autosomal recessive due to consanguinity. Routine laboratory investigations were normal in all family members tested. The total content of mucopolysaccharides, sialic acid and hexosamine in biopsed tissue was significantly lower than normal. Our findings demonstrate that a defect in glycoprotein synthesis, possibly enzymatic, may be the cause of lipid proteinosis and its protean clinical manifestations. Copyright Copyright 1999 S. Karger AG, Basel

Abstract: The aim of our study was to verify the in vitro growth of Staphylococcus epidermidis in various dilutions of some viscoelastic substances containing hyaluronic acid (Healon and Healon GV, IAL, Biolon). Serial twofold dilutions of each sterile viscoelastic substance, prepared so as to obtain a final concentration ranging from 50 to 0.78% of the product in sterile saline solution (0.85% NaCl), were taken out with a pipette that delivered 1.0 ml/tube. One hundred microliters of the S. epidermidis inocula, used for the evaluation of the positive control of the test organism, was dispensed into each tube. After 24 h of aerobic incubation at 37 degrees C, 100 microl of sample was taken out from each tube and plated into the specific medium for the growth of the test organism. After 24 h of incubation at 37 degrees C, these agar plates were examined and the colony-forming unit count of the test organism was compared to the corresponding total colony count, acting as a positive control, in order to determine the quantitative variation of the test organism grown in the presence of the viscoelastic compounds. For the lowest dilutions (from 1:2 to 1:8) statistically significant bacterial growth was detected in all tested viscoelastic substances. For the highest dilutions (1:64 and 1:128) Biolon and Healon GV showed a significant inhibition of S. epidermidis growth. A significant inhibition was also observed in the highest dilution (1:128) of Healon. In every dilution of IAL a statistically significant increase in bacterial growth was observed. It remains to be carefully considered whether S. epidermidis, accidentally penetrating the eye via the intraocular lens, could find a culture medium in a small amount of sodium hyaluronate left in the capsular bag behind the optic.

Abstract: A study was performed to detect the presence of polycyclic aromatic hydrocarbons (PAHs) in bovine eyes. Twenty fresh bovine eyes were used to detect the presence of PAHs in lens, vitreous and aqueous by HPLC and spectrofluorometer. In lenticular tissue the mean amount of PAHs was 0.0271 microgram/g and the mean level of PAH in each lens was 0.059 microgram. Five types of PAHs (pyrene, fluoranthene, triphenylene, 1.2-benzanthracene and chrysene) were found in the lenses but none in vitreous and aqueous. These data indicate that PAHs are present only in the lens of the bovine eye. The source of these substances in mammalian clear lens is unclear.

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Abstract: BACKGROUND: Ketanserin is a specific antagonist of 5-HT2 and 5-HT1c receptors. These receptors are linked to the stimulation of phosphoinositide metabolism and are involved in IOP controls. Orally and topically administered ketanserin reduces IOP in normotensive and glaucomatous eyes. METHODS: Ketanserin 0.5% eye drops were administered to 20 patients with primary open-angle glaucoma in a randomised, crossover, double-masked fashion to evaluate the effect of ketanserin in glaucomatous patients already receiving timolol who did not have controlled IOP (> 21 mmHg). Mean and range of IOP curve (8.00 a.m.-8.00 p.m.), pupil diameter, Schirmer I, basal secretion test and BUT values were recorded at baseline and after 2 weeks of topical administration of ketanserin or placebo twice daily. The alternative treatment was given 2 weeks later and the same protocol was repeated. RESULTS: When patients received placebo no significant variations were found in the analysed parameters. Ketanserin significantly reduced mean IOP (19.5%) and was effective for up to 12 h without inducing variations of tear secretion or pupil diameter. No systemic side effects were observed, and no significant variations in ocular symptoms and signs were reported. CONCLUSION: These results indicate that topical administration of ketanserin may be useful to reduce IOP in patients not controlled with beta-blockers.

Abstract: Fifty male albino rabbits were studied. Ten animals served as controls. Forty animals were prepared to receive photorefractive keratectomy (PRK), including anesthesia, scraping of the corneal epithelial cells, etc. Twenty of these animals then received PRK with energy delivered by excimer laser (pulse rate = 20 Hz, fluence 250 mJ/cm2; number of pulses = 6032; cumulative UV dose = 1508J/cm2). The other 20 animals were exposed to the same operating microscope light as the PRK-treated animals, but they did not receive PRK. All three groups were divided into halves: the first half was immediately analyzed at 0 time, and the second half was observed 1 year later. Samples of aqueous humor and lens were analyzed. The levels of reduced and oxidized glutathione, hydrogen peroxide, ascorbic acid, and malondialdehyde were determined. Excimer laser-induced ultrastructural modifications of the lens, verified through scanning electron microscopy, were studied at the same intervals. Immediately after PRK, the biochemical parameters studied, both in aqueous humor and in lens of treated animals, showed significant differences. One year later, the observed biochemical variations in lens were still present, whereas aqueous humor values did not significantly differ from control values. Ultrastructural abnormalities of the lens appeared only 1 year after PRK In the animals that received only the preparation for PRK the biochemical and ultrastructural differences did not significantly vary as compared to the data obtained from control animals. These findings suggest that the biochemical and ultrastructural lens alterations induced by PRK may represent events relevant to cataractogenesis in the rabbit.

Abstract: Twenty male albino rabbits were studied. Four animals served as controls; the remaining 16 animals represented the treated group. All the treated animals were exposed to the same amount of energy delivered by the excimer laser (pulse rate: 20 Hz, fluence 250mJ/cm2; number of pulses: 6032; cumulative UV dose 1508 J/cm2) and were divided into eight groups of 2 animals each (four eyes). Samples of aqueous humor and lens were obtained at the following intervals: 5, 10, 20 and 40 min and 1, 2, 3 and 4 weeks after photorefractive keratectomy (PRK). The levels of reduced and oxidized glutathione, hydrogen peroxide, ascorbic acid and malondialdehyde were determined. Aqueous humor analyses, twenty min after PRK, showed no significant differences with pre-treatment values, while the observed variations in lens were constantly present over the entire follow-up period (one month). These findings suggest that the biochemical lens alterations induced by PRK may represent the earliest events relevant to cataractogenesis in the rabbit.

Abstract: PURPOSE: In this investigation the authors studied the effect of dapiprazole, an alpha-adrenergic blocking agent, on aqueous humor dynamics in patients affected with pigmentary glaucoma. METHODS: Dapiprazole 0.5% eye drops were administered 3 times daily as adjunctive therapy to 16 pigmentary glaucoma patients in addition to timolol 0.5% eye drops twice daily. Computerized tonography was performed before and 3, 12 and 36 months after dapiprazole treatment. Sixteen sex- and age-matched pigmentary glaucoma patients treated with timolol 0.5% eye drops alone were used as a control group. RESULTS: After 36 months of follow-up, the dapiprazole-treated group showed a significant increase in total outflow facility (C, from 0.17 +/- 0.04 to 0.22 +/- 0.07 ml min-1 mm Hg-1; p = 0.010, paired t test) and Po/C ratio (Q) significantly decreased from 113.39 +/- 31.02 to 89.22 +/- 51.66 (p = 0.036, paired t test). CONCLUSIONS: Our results show that the introduction of dapiprazole in the therapy of pigmentary glaucoma may be useful in the long-term management of these patients. Its mechanism of action is likely to be due to iridoplegia; in fact, a decrease in the shedding of pigment occurs, with time, the outflow facility increases and the pigment clearance from the trabecular meshwork is enhanced.

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Abstract: The objective of this study was to test bacteria ability to use Na-hyaluronate as a nutrient in vitro. Thirteen bacteria strains were tested in three different media: specific culture medium, agar-Healon medium and agar-Healon GV medium. The bacterial growth criteria were determined by counting the number of new colonies appearing at each observation time (0, 24, 48 and 72 h). The results were expressed as the percentage of growth in agar-Na-hyaluronate compared to each corresponding specific culture medium. After 24 h in the medium containing agar-Healon, S. aureus, S. epidermidis, S. pyogenes and S. viridans grew using hyaluronic acid as a nutrient. The percentage of growth of these species remained constant over the follow-up period. The other bacteria strains tested were unable to use Healon as a nutrient. After 24 h of incubation in the medium containing agar-Healon GV, S. aureus, S. epidermidis, S. pyogenes, and S. viridans exhibited about 20% growth. Subsequently, this percentage slowly increased to about 50%. The other bacteria stains tested were unable to employ Healon GV as a nutrient. With the exception of Staphylococci and Streptococci, the other species do not synthesize the necessary enzymes to break glucosidic bonds, therefore neither concentration of hyaluronic acid can be utilized as a source of carbohydrate for their survival in culture media.

Abstract: The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound.

Abstract: It was evaluated whether ArF 193 nm excimer laser corneal surgery represents a risk factor in cataractogenesis. For this purpose, 20 male albino rabbits underwent a photorefractive keratectomy and biochemical analyses on aqueous humour (hydrogen peroxide, ascorbic acid, and reduced and oxidized glutathione) and on lens (malondialdehyde, reduced and oxidized glutathione) were performed. In the aqueous humour of all treated animals a significant increase in hydrogen peroxide and in oxidized glutathione and a concomitant decrease in ascorbic acid and reduced glutathione concentration were observed. Moreover, all these variations were significantly correlated with the cumulative UV dose used. In the lens, after excimer laser corneal surgery, there was a dramatic loss of reduced glutathione and a parallel increase in oxidized glutathione levels. Malondialdehyde concentration was also increased, but only at the highest UV exposure. Moreover, all these variations were significantly correlated with the cumulative UV dose used. These findings demonstrate that the exposure of aqueous humour and lens to the secondary radiation generated after ArF 193 nm excimer laser corneal photoablative keratectomy induces biochemical modifications which are known to be markers of cataractogenesis.

Abstract: The effect of topical ketanserin on intraocular pressure (IOP) in normotensive and hypertensive eyes was evaluated. The study was performed on 10 healthy volunteers and 10 glaucomatous patients. Systolic arterial blood pressure (SBP), diastolic arterial blood pressure (DBP), heart rate (HR), IOP, tonographic outflow facility, pupil diameter, corneal thickness, and tear secretion were recorded at baseline and at 1 hour intervals for 12 hours after topical administration of 0.5% ketanserin or placebo, given in a randomised, double masked, crossover fashion. The alternative treatment was given 1 week later. In all subjects ketanserin significantly lowered IOP, while no variations in SBP, DBP, HR, pupil diameter, corneal thickness, and tear secretion were found. When subjects received placebo no significant variations of IOP occurred. Total outflow facility, measured by conventional tonography, increased significantly after drug administration in all subjects. Ketanserin is effective up to 6 hours in control subjects and 9 hours in glaucomatous patients. The placebo did not induce any change in this component of the aqueous humour dynamic in normal or in glaucomatous eyes. The findings indicate that topical ketanserin might be added to the list of antiglaucomatous agents.

Abstract: Authors report on the effect of reduced glutathione parenterally administered on the anemic status in patients suffering from chronic renal failure and undergoing hemodialysis. Twenty patients were studied for 180 days and were divided into two age- and sex-matched groups. The first group (10 patients) received placebo, the second group (10 patients) received the treatment (1,200 mg of reduced glutathione). Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure.

Abstract: Eye involvement in chronic myeloid leukemia is well known. The signs are infiltration of the choroid, the sclera, the episclera, the conjunctiva and the optic nerve. Eye involvement is more common in acute than in chronic forms of leukemia. This paper reports a case of chronic myeloid leukemia in which optic nerve involvement was the only initial sign of the disease.

Abstract: We report the presence of lens opacities in patients with prolactin-secreting microadenomas of the pituitary gland. The occurrence of lens opacities was related to prolactin serum levels and appeared only in women. The mechanism by which prolactin induces cataract is not known, although this hormone could affect the lens's permeability to ions, water, sugars, and amino acids. Moreover, the lens opacities found in women but not in men seem to indicate synergism with estrogens.

Abstract: The authors report on the occurrence of ocular abnormalities in X-linked ichthyosis (XLI) patients, in their carrier mothers and in healthy volunteers who served as controls. The diagnosis of XLI was based on: (1) demonstration of steroid sulfatase deficiency in cultured skin fibroblasts; (2) lack of hybridization of patient's deoxyribonucleic acid (DNA) with specific steroid sulfatase complementary DNA probe; (3) electrophoretic mobility of plasma lipoproteins. Cholesterol sulfate plasma levels were also determined. The incidence of corneal opacities was the same in XLI patients and in their carrier mothers (23.7 and 24.3%, respectively). Neither other corneal nor ophthalmological alterations were found. Moreover, in XLI patients the plasma levels of cholesterol sulfate were about twenty times higher than in controls. Our findings demonstrate that ocular changes do not seem to be an absolute criterion for a definite diagnosis of XLI and the fact that the pathogenesis of corneal opacities is not due to an accumulation of cholesterol sulfate, but rather that this compound probably induces physicochemical changes of the corneal tissue properties.

Abstract: Since many years experimental evidences have suggested an association between nutrition and lens opacities. A dietary deficiency of antioxidants and reactive oxygen scavengers may be involved in the pathogenesis of the "idiopathic" human senile cataract, as it has been demonstrated in some experimental cataracts. We tested the levels of ascorbic acid (vit. C), alpha-tocopherol (vit. E), reduced glutathione (GSH) and malondialdehyde (MDA) in the plasma or in the red blood cells (RBC) of 42 patients who were affected by surgically significant cataract and of 40 age-matched controls. Plasma vit. C mean level was 4.46 gamma/ml in cataracts and 4.62 gamma/ml in controls, while vit. E level was 7.70 and 7.09 gamma/ml respectively. RBC GSH was found to be 342 gamma/ml in cataracts and 346 in controls, while the MDA content was 4.06 picoMol/ml and 4.08 picoMol/ml respectively. The level of each tested nutrient or metabolite was not found to be statistically different between cataractous patients and controls, nor any significant trend was found to be present when the nutrients and metabolites were correlated to each other. Our results do not support the hypothesis of a nutritional deficiency in human senile cataracts. However, a defect in the antioxidative metabolism pathways could be present either systemically or at lens level.

Abstract: The effectiveness of a new visual field analyzer, the Takagi Automatic Tangent Screen ATS-85, in detecting glaucomatous patients was studied. The study population consisted of three groups of subjects: normal healthy volunteers, glaucomatous patients with defective visual fields, and glaucomatous patients with early visual-field defects. Our results indicated that the screening program of the ATS-85 could be a useful instrument particularly for epidemiologic investigations.

Abstract: Intraocular pressure, aqueous flow, outflow facility, outflow resistance, and both corneal and lens thickness were measured in patients receiving regular hemodialysis three times a week to test for induced variations of these parameters. No statistically significant differences occurred in any of the measurements taken. This study confirms that patients undergoing hemodialysis are not susceptible to glaucomatous disease.

Abstract: We evaluated the effect of the antihypertensive drug ketanserin, a 5-HT antagonist, on intraocular pressure (IOP) in 20 patients with ocular hypertension. IOP, pupil diameter, systolic arterial pressure (SBP), diastolic arterial pressure (DBP) and heart rate (HR) were recorded at baseline and at 1-hr intervals for 3 hr after oral administration of 20 mg ketanserin or placebo, given in a randomized, double masked, cross-over fashion. The alternative treatment was given a week later. In all patients, ketanserin significantly lowered IOP and SBP, while no variations in pupil diameter, DBP and HR were found. Moreover, after drug administration, total outflow facility, measured by conventional tonography, increased significantly. These findings indicate that oral ketanserin could represent a new antiglaucomatous drug.

Abstract: Cigarette smoke contains detectable amounts of cyanide, regardless of the type of cigarette. The very high levels of this compound in plasma of amblyopic smokers suggests that cyanide causes optic neuropathy. The detoxification of cyanide in man occurs through various metabolic pathway; the most important are those that use sulfur to transform cyanide into thiocyanate. One of the richest sources of reduced sulfhydryl groups is reduced glutathione (GSH). For this reason we investigated red cell GSH levels in non-smokers, in healthy smokers and in smokers affected by optic neuropathy to ascertain whether this compound is a marker of the disease. Red cell GSH levels in the non-smokers group were similar to those of affected smokers. On the contrary, GSH levels in healthy smokers were significantly more elevated. During therapy with vitamin E we noted that the concentration of GSH decreased with the progression of the disease and increased with recovery. Moreover, there was a good correlation between GSH levels and clinical findings. Our findings demonstrate that GSH plays a key role in the detoxification of cyanide and so it could be a marker of tobacco smoke-induced optic neuropathy.

Abstract: The oxidative state of glutathione in red blood cells (RBC) and plasma of diabetic patients and of age-matched volunteers has been studied. Oxidized glutathione (GSSG) levels in plasma from diabetic subjects were higher than those from controls (17.2 +/- 2.5 and 3.3 +/- 0.4 micrograms/ml, respectively). This phenomenon was evident also in in vitro experiments: incubated RBC from diabetic patients released very high amounts of GSSG in medium. Thus, erythrocytes are responsible for the enhanced amounts of GSSG found in plasma from diabetic patients. The fall in the conversion of GSSG to reduced glutathione in RBC could be due to a reduced activity of the glucose-6-phosphate dehydrogenase (G6PDH) enzyme which has been observed in diabetic patients. In this way, G6PDH supplies reduced amounts of NADPH to the glutathione reductase enzyme affecting the integrity of the glutathione system; on the other hand, the activation by glucose of the polyol pathway also reduces the levels of NADPH for the glutathione reductase enzyme.

Abstract: Reduced and oxidized glutathione levels in red blood cells and plasma from humans were determined after oral vitamin E treatment. The experiments confirmed that vitamin E enhances reduced glutathione levels in red blood cells. Moreover, vitamin E supplement resulted in a significant reduction of the plasma oxidized glutathione content. Thus, it seems that the effect of vitamin E on the reduced glutathione content is not exerted via direct modulation of the glutathione-synthesizing enzymes, but rather by a more general mechanism of preserving reduced glutathione consumption by reducing the burden of the glutathione system.

Abstract: This report presents the results of a study designed to verify the influence of lens opacities on the visual field indices. Four age-matched groups of subjects were considered: healthy volunteers, glaucomatous patients without lens opacities, cataractous patients without glaucoma and glaucomatous patients with lens opacities. The quantification of lens opacities was performed with the Lens Opacity Meter 701 instrument. The visual field indices were obtained automatically from the G1 program of the Octopus system. The statistical analysis of the results (coefficient of correlation) has shown that only the visual field indices that correspond to uniform and diffuse loss of light sensitivity were influenced by the presence of cataract. On the contrary, the visual field indices that indicate local irregularities of the threshold were not significantly influenced by the presence of lens opacities.

Abstract: In this study we have investigated the oxidative metabolism of red cells (RBC), plasma, serum and aqueous humour of healthy subjects and of age-matched cataractous patients with and without chronic renal failure (CRF). Reduced glutathione (GSH) levels in RBC were lower in CRF patients than in the other groups. Oxidized glutathione (GSSG) plasma levels in CRF patients were higher than those of controls and cataractous subjects. The activity of the enzyme glucose-6-phosphate dehydrogenase in RBC was significantly reduced in CRF patients with respect to the other two groups. The levels of malondialdehyde (MDA) in RBC and in lens were about twice in CRF patients compared with the other two groups. The plasma levels of vitamin E were diminished in CRF patients; on the contrary, the biological liquid oxidant activity (BLOA) of serum in CRF patients was significantly higher than in controls and in cataractous patients without CRF. Cataractous patients with and without CRF showed similar levels of GSH in aqueous humour; on the contrary, the content of GSSG was significantly higher in CRF patients. Our findings seem to demonstrate that CRF patients are exposed to oxidative stresses that could probably act synergistically with uraemia and carbamylation of lens proteins. This synergism could explain why CRF represents a relatively high risk factor for cataract.

Abstract: There is evidence that some antihypertensive drugs, such as beta blockers, are effective in reducing intraocular pressure (IOP) and are commonly used in the medical treatment of glaucoma. The aim of this study was to evaluate the effects of the anti-serotonergic agent ketanserin, which has associated alpha 1-blocking properties, on IOP in normotensive and hypertensive eyes. The first part of the study was performed in six arterial hypertensive patients (mean +/- SD blood pressure 156/102 +/- 10/6 mmHg) with a pretreatment IOP in the normal range (15.7 +/- 1 mmHg). Both blood pressure and IOP were measured at baseline and at 1 hour intervals up to 3 hours following the oral administration of ketanserin 20 mg or placebo, given in a randomized manner. Three hours after ketanserin treatment, mean systolic and diastolic blood pressures dropped by 10/5 mmHg and mean IOP was reduced by 2.7 mmHg; after placebo, no change was observed in these variables. Thereafter, four normotensive patients with chronic open-angle glaucoma (IOP = 22.8 mmHg) were given 20 mg ketanserin orally. Three hours after administration, a 22% reduction in mean IOP occurred (-5.8 mmHg), with a concomitant reduction in mean systolic blood pressure of 13.0 mmHg. These results indicate that ketanserin treatment reduces IOP and systemic blood pressure. Further, long-term studies are needed in order to confirm the efficacy of ketanserin in the medical treatment of ocular hypertension.

Abstract: Intraocular pressure (IOP) in a healthy population residing in the urban area of Naples, Italy was measured. The IOP was recorded in the early morning. A total of 751 subjects (367 men and 384 women) (1502 eyes) was examined twice on two different days using a Goldmann tonometer mounted on a Haag-Streit slitlamp. Age ranged from 6 to 89 years. We found a slight and not significant IOP increase with age and that the age-related IOP increase was more evident in women.

Abstract: Lens opacity was quantified in 85 cataractous patients, using a new instrument: the lens opacity meter 701 (LOM; Interzeag, Schlieren, Switzerland). Cataracts were classified as nuclear, cortical, subcapsular and mixed forms. Sensitivity, specificity and reproducibility of the results were evaluated by statistical analysis. Visual acuity was correlated with LOM values in patients with nuclear and mixed cataracts. Moreover, the instrument gave a good degree of reproducibility only in patients who presented these forms of lens opacities. Our findings demonstrate that the LOM 701 is able to detect and to measure only lens opacities which affect the central area of the lens.

Abstract: Authors describe the in vitro effect of bendazac-L-lysine salt on the activity of enzyme aldose reductase from rat lens. In the presence of bendazac the activity of the tested enzyme was inhibited. Lineweaver-Burk plot demonstrated that the inhibition was noncompetitive. The possible curative effects on diabetic cataract together with a better way of administration are pointed out.

Abstract: Lens aging has been measured in vivo using a new instrument: the lens opacity meter 701 (Interzeag, Schlieren, Switzerland). Statistical analyses have been performed to verify the occurrence of the phenomenon, the sex differences and the reproducibility of the obtained results. The findings demonstrate an increase in the light scattering in the normal lens with aging, which is similar in both sexes. The instrument detects this process and the measurements have a high degree of reproducibility.

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Abstract: The authors have investigated the oxidative state of glutathione in red blood cells (RBC) and plasma from patients affected by chronic renal failure (CRF) and from age-matched healthy subjects. RBC-reduced glutathione (GSH) levels were significantly lower in CRF patients than in healthy subjects. Oxidized glutathione (GSSG) levels in plasma from CRF patients were higher than in plasma from controls. GSSG levels in RBC were similar in both groups. No differences were noted in GSH plasma levels between patients and controls. The GSSG/GSH ratios in RBC were similar in the two groups; on the contrary, the GSSG/GSH ratio in plasma was significantly higher in CRF patients. High levels of GSSG in plasma could exert two important effects on RBC: (1) inhibition of glucose-6-phosphate dehydrogenase activity, with a consequent alteration of the glutathione system; (2) GSSG easily reacts with hemoglobin to produce hemoglobin-glutathione mixed disulfides, with a consequent protein aggregation and precipitation. In vitro experiments have shown that RBC from CRF patients easily lyse when incubated with their same plasma, but not when incubated in saline buffer. Our results seem to demonstrate that plasma from CRF patients contains various oxidants which could affect the integrity of the glutathione system in RBC. This alteration could play a role in the pathogenesis of anemia in uremic patients.

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Abstract: In this study we have investigated the oxidative metabolism of red blood cells (RBC), plasma, serum, aqueous humor, and lens of healthy subjects and of age-matched cataractous patients with and without diabetes. Reduced and oxidized glutathione (GSH GSSG) levels in RBC were similar among the three groups. Plasma levels of GSSG were higher in diabetics than in cataractous and control subjects. No differences in plasma content of GSH were noted among the three groups. The activity of the enzyme glucose-6-phosphate dehydrogenase was significantly diminished in diabetic patients. Controls and cataractous patients showed similar levels of malondialdehyde (MDA). Although not significant the MDA content in RBC from diabetics was elevated. No differences in plasma levels of vitamin E were noted among the three groups. The biological liquid oxidant activity of serum in diabetic patients was significantly higher than in controls and cataractous patients. GSH levels in aqueous humor were similar in diabetic and nondiabetic cataractous patients. The content of GSSG in aqueous humor was highest in diabetic patients. Control clear lenses showed low levels of MDA. The MDA levels in cataractous lenses from nondiabetic patients were significantly higher than those of controls. In diabetic patients the content of MDA in the lens was approximately twice as high as the cataractous values. Our results seem to demonstrate that oxidative damage could play a role in the pathogenesis of cataract in diabetes.

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Abstract: Reduced (GSH) and oxidized (GSSG) glutathione levels in arterial and venous rabbit red blood cells (RBC) and plasma are reported. No significant differences were noted between arterial and venous erythrocytes GSH and GSSG content. Plasma GSH levels were found to be the same in both arterial and venous samples. Contrarily, the concentrations of GSSG were higher in venous than in arterial plasma. These findings cannot be attributed solely to the increased RBC oxidative activity that occurs in the venous system. The phenomenon may reflect the oxidative state present in other tissues and may thus be a harbinger of differences in GSH content.

Abstract: The effects of topical administration of glucocorticoids on rabbit lenses are described. Animals were divided into three groups. The first group (A) served as control, the second (B) and the third (C) group were treated with betamethasone and fluorometholone, respectively. After 40 days of treatment there was a significant fall in the levels of nonprotein sulfhydryl (-SH) groups (group A: 3.82 +/- 0.21; group B: 2.61 +/- 0.11; group C: 1.93 +/- 0.13 mumol/lens) and of protein -SH groups (group A: 8.215 +/- 1.023; group B: 4.120 +/- 0.631; group C: 4.068 +/- 0.538 mumol/lens). Also ascorbic acid levels showed a significant decrease both in lens and in aqueous humor. No differences were noted in the reduced glutathione content in aqueous humor. The fall in nonprotein and protein -SH could be the first event in the well-known biochemical changes that occur in steroid-induced cataract. The mechanism underlying steroid-induced damage could be due to a conformational change of lens crystallins which results in an unmasking of -SH groups with a consequent increased susceptibility to oxidation. The decrease of ascorbic acid should represent an effect of the fall in the glutathione system. Lastly, it is hypothesized that the protective effect exerted by some substances, such as vitamin E and ascorbic acid, occurs by counteracting this oxidation.

Abstract: High doses of orally administered vitamin E have been given to humans, rabbits and rats. Placebo has been given to control groups. At the end of the treatment period, enhanced levels of reduced glutathione (GSH) were found in the red blood cells (humans and rabbits), aqueous humor (humans and rabbits) and lens (rabbits and rats) of treated subjects and animals. The percentage of GSH converted to oxidized glutathione (GSSG) was the same in both vitamin E-supplied and control groups. The GSSG--GSH ratio remained unchanged. The plasma levels of vitamin E were significantly higher in treated than in control subjects and animals. At the end of the study, the levels of vitamin E in aqueous humor and lens of rabbit were the same in animals which received vitamin E and in animals which received placebo. Lastly, vitamin E administration did not influence ascorbic-acid levels in plasma (humans and rabbits), aqueous humor, lens and vitreous body (rabbits).

Abstract: High doses of parenterally administered vitamin E (30 mg/kg/die) have been given to albino rabbits. We have found a significant elevation of red blood cells reduced glutathione, while the percent level of oxidized versus the reduced form falls from 2% to 1.3%. This finding could be explained with an elevation of the synthesis of this tripeptide, depending on the stimulation of glutathione-synthetase activity. On the other hand, a reduced utilization of this tripeptide for the free radicals detoxifying activity could be claimed for.

Abstract: High doses of orally administered vitamin E (1000 IU/day) have been given to ten normal volunteers. Ten control subjects received placebo. Red blood cell glutathione was significantly higher in treated subjects than in the controls (controls: 267.5 +/- 15.7 micrograms/mL; treated: 374.8 +/- 17.3 micrograms/mL). These findings could be explained by an increase of glutathione synthesis brought about by the stimulation of glutathione synthetase activity. An alternative possibility is a reduced utilization of glutathione for the detoxification of free radicals. These two mechanisms could be effective in counteracting the glutathione content feedback of the synthetizing enzymes.

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Abstract: Red cell glutathione has been assayed in a family affected by Leber's optic atrophy. The results are in agreement with a defective cyanide metabolism. The transmission mechanism of the disease is discussed. Lastly, a preventive and therapeutic approach is proposed.

Abstract: 22% of a group of adult Neapolitans were found to have persistent high lactase activity, and 16% were lactose absorbers as indicated by measurement of breath hydrogen concentration and rise in blood glucose after oral lactose administration. Among adults in the same area with idiopathic senile or presenile cataract 49% were identified as lactose absorbers with the breath hydrogen test and 55% by the rise in blood glucose. These results suggest that adults able to absorb galactose from a lactose-containing diet are especially susceptible to senile or presenile cataract.