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Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervations, leading to a reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism and mitosis of epithelial cells, with subsequent deficiency in epithelial repair, stromal and intracellular oedema, loss of microvilli, and abnormal development of the basal lamina. Several recent studies have proposed different therapies based on different aetiopathogenetic theories. The aim of the therapy is to treat aetiopathogenesis and, at the same time, promote corneal healing. In this paper, we report the aetiology, diagnosis, management, and medical and surgical treatment of NK, also indicating future treatments based on the most recent studies., (© 2013 S. Karger AG, Basel.)

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., (Copyright 2004 S. Karger AG, Basel)

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., (Copyright 2003 S. Karger AG, Basel)

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., (Copyright 2000 S. Karger AG, Basel.)

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 1999 S. Karger AG, Basel)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.