Pilot study to evaluate the efficacy and safety of pneumatic trabeculoplasty in glaucoma and ocular hypertension.

PURPOSE: Following laser-assisted in situ keratomileusis (LASIK), intraocular pressure (IOP) is measurably lower in a significant number of cases. It has been proposed that the decrease in IOP may be a real event. Prior trials have evaluated pneumatic trabeculoplasty (PNT) in combination with concomitant glaucoma medications. The aim of this study was to determine the efficacy and the safety of PNT alone to lower IOP in patients with primary open angle glaucoma (POAG) or ocular hypertension (OH). METHODS AND RESULTS: A total of 37 subjects with POAG or OH were enrolled in a prospective, open-label, fellow-eye, multicenter trial to determine the IOP lowering effects of PNT. All subjects underwent ophthalmologic examinations and IOP measurements and were washed out from all glaucoma medications prior to the start of the study. The trial was intrapatient controlled for the first 30 days, with one eye receiving PNT at days 0 and 7 and the fellow eye serving as the control. The second eye was treated with PNT at day 30. The patients were followed for 120 days, with the first eye receiving an additional PNT treatment at days 90 and 97. Two analyses-an intent to treat analysis in which the last IOP measurement for patients dropped from the study was carried forward and an analysis including only those patients who completed the trial-were performed. Of the 37 patients enrolled, 27 (73%) completed the study. For the intent to treat analysis the baseline mean IOP was 24.7+/-1.9 mmHg for eye 1 and 23.6+/-2.3 mmHg for eye 2 and the difference was statistically significant (p<0.05). Using this analysis the differences between eye 1 mean IOP at days 1, 7, 14, and 60 and the baseline mean IOP were statistically significant (p<0.05). The differences between eye 2 mean IOP and the baseline mean IOP were statistically significant (p<0.05) at all time points except day 14 and day 30. The greater mean IOP reductions from the baseline mean IOP for eye 1 were at study day 1 (-16,1%), day 14 (-9%), and day 60 (-8.9%). For eye 2 they were at day 60 (-8.7%) and at day 120 (-9.1%). For the analysis that included only those subjects who completed the trial the decrease in eye 1 mean IOP from baseline was statistically significant (p<0.05) at all time points. The decrease in eye 2 mean IOP from baseline was statistically significant at all time points except day 30. Using this analysis the greater mean IOP reductions from the baseline mean IOP for eye 1 were at study day 1 (-19%), day 14 (-15.7%), day 37 (-16.3%), day 60 (-20.0%), day 90 (-18.1%), day 97 (-16.8%), and day 120 (-15.8%). For eye 2 greater mean IOP reductions from baseline mean IOP were seen on day 37 (-13.0%), day 60 (-16.7%), day 90 (-15.5%), day 97 (-14.5%), and day 120 (-7.2%). No statistically significant differences were found in mean IOP reduction between the two eyes treated. A total of 34 patients (92%) showed adverse effects: conjunctival hyperemia in 26 (70.3%) and conjunctival hemorrhage in 14 (37.8%). CONCLUSIONS: This pilot study of PNT showed a potentially good IOP lowering effect on glaucoma and hypertensive patients. Additional studies would help to better define the types of patients who respond to PNT and to identify risk factors that may lead to treatment failure.

Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.

The aim of this randomized, double-blind, placebo-controlled clinical trial was to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus alterations in early age-related macular degeneration (AMD). One hundred and six patients with a clinical diagnosis of early AMD were randomized to the treated or control groups. The primary efficacy variable was the change in the visual field mean defect (VFMD) from baseline to 12 months of treatment, with secondary efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal sensitivity as measured by perimetry, and fundus alterations as evaluated according to the criteria of the International Classification and Grading System for AMD. The mean change in all four parameters of visual functions showed significant improvement in the treated group by the end of the study period. In addition, in the treated group only 1 out of 48 cases (2%) while in the placebo group 9 out of 53 (17%) showed clinically significant (>2.0 dB) worsening in VFMD (p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes was also statistically significant as compared to placebo when either the most affected eyes (p = 0.045) or the less affected eyes (p = 0.017) were considered. These findings strongly suggested that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early AMD.

Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study.

Recent histopathologic studies have shown that mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in the pathophysiology of age-related macular degeneration (AMD). We supposed that compounds which improve mitochondrial functions (mitotropic compounds) may show beneficial effects in preventing AMD. Fourteen patients affected by early AMD were treated with a mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs), coenzyme Q10 (CoQ10) and vitamin E, while an equal number of age- and sex-matched patients affected by early AMD were treated with vitamin E only. Recovery time after macular photostress, foveal sensitivity and mean defect in the visual field as well as blood lipid levels were recorded at the beginning and after 3, 6, 9, 12 and 24 months of follow-up. In the treated group, all the visual functions showed slight improvement which was evident after 3 months of treatment and remained nearly stationary by the end of 24 months. The same tests in the control group showed slow worsening. The divergence between treated and control groups became more marked with time, but the difference was not significant at any time of the follow-up. These findings suggest that the blend of ALC, PUFA, CoQ10 and vitamin E may improve retinal functions in early AMD.

MTHFR C677T mutation, factor II G20210A mutation and factor V Leiden as risks factor for youth retinal vein occlusion.

OBJECTIVE: To determine whether methylene tetrahydrofolate reductase (MTHFR) C677T mutation, factor II G20210A mutation and factor V Leiden are risk factors for retinal vein occlusion (RVO) in patients under fifty years of age. METHODS: Comparison of 29 patients, under 50 years old of age, as affected RVO and 62 age matched normal controls. Plasma MTHFR C677T genotype, Factor II G20210A genotype, Factor V Leiden genotype, S protein level, C protein level, APCR presence (Actived Protein C Resistance), homocysteine level and Beta-thromboglobulin level were determined. RESULTS: Seventeen RVO patients and twenty-one controls were heterozygous for the MTHFR C677T mutation. Three RVO patients and twenty-three controls were homozygous for the MTHFR C677T mutation. Three RVO patients and two controls were heterozygous for the factor II G20210A mutation. One control was heterozygous for the factor V Leiden. CONCLUSIONS: This study fails to demonstrate that these mutations are risk factors for RVO in patients under fifty years of age.

A new method of biofeedback in the management of low vision.

Twenty-eight patients with low vision were enrolled into the study. A preliminary study was carried out on 18 eyes of 13 patients with low vision who underwent visual rehabilitation with a new instrument for biofeedback (BF) applied to vision; improved biofeedback integrated system (Ibis). Successively, eight patients (16 eyes) with bilateral low vision were subjected to biofeedback in one eye. The experimental and control eye were evaluated separately. Then a placebo training was developed on seven patients (12 eyes). Visual acuity, colour vision, automated perimetry, contrast sensitivity and flash VEP were evaluated. A brief review of the literature and the possible mechanisms behind the results are discussed.

Element concentrations and cataract: an experimental animal model.

The determination of inorganic ions in cataractous human lenses has been the subject of several investigations; nevertheless, few studies have been concerned with trace element contents in lenses, and data are sometimes contradictory. An animal experimental model of induced cataract is here proposed with the aim of evaluating the changes of Ca, Na, K, Cu and Zn concentrations. The cataract was produced by an Nd:YAG Laser treatment of the right eye of sexteen male rabbits. The determination of the elements was performed by atomic absorption spectrometry (both flame and flameless methods) after an acid digestion of samples. Compared with the results obtained in left lenses used as a control (Ca 14.4+/-5.7 mg/kg d.w.; Na 1.3+/-0.5 g/kg d.w.; K 9.9+/-1.1 g/kg d.w.; Cu 0.24+/-0.09 mg/kg d.w.; Zn 24.8+/-2.3 mg/kg d.w.), the mean concentration values of opaque lenses showed some significant changes for Ca, Na, and Cu (Ca 123.7+/-106.6 mg/kg d.w.; Na 4.5+/-4.3 g/kg d.w; Cu 0.43+/-0.21 mg/kg d.w.). Potassium showed a tendency to decrease, and zinc to increase. Positive correlations were found between calcium and sodium both in controls (r=0.73, p<0.001) and in treated lenses (r= 0.87, p<0.0001). An inverse correlation between Ca and K confirmed the tendency of potassium to decrease.

Optic neuropathy in systemic lupus erythematosus and antiphospholipid syndrome (APS): clinical features, pathogenesis, review of the literature and proposed ophthalmological criteria for APS diagnosis.

Optic neuropathy is a well-known ocular manifestation occurring in patients with systemic lupus erythematosus (SLE), and it remains one of the major causes of blindness in these patients. We report data from six SLE patients with optic neuropathy, one of whom was considered to have antiphospholipid syndrome (APS). This patient had monolateral optic neuropathy, whereas the other five SLE patients had bilateral optic nerve disease. We believe that the monolateral occurrence of optic neuropathy in our patient can be considered as a 'focal' neurological disease due to a thrombotic event involving the ciliary vasculature. Conversely, bilateral optic nerve damage in SLE could be considered to be a 'general' neurological disease due to different immunological mechanisms, such as vasculitis. Additionally, the literature on SLE patients affected by optic neuropathy is reviewed to evaluate the major clinical features, particularly neurological features. In reviewing the literature, it appears that bilateral optic neuropathy in SLE occurs more frequently than monolateral optic neuropathy, and the main neurological manifestation seen in these patients is transverse myelitis, particularly in SLE patients with bilateral optic nerve disease. Finally, we propose a clinico-ophthalmological spectrum of APS and outline the ocular clinical manifestations that can be considered as diagnostic for the syndrome.

Catecholaminergic nerve fibres in normal and alkali-burned rabbit cornea.

BACKGROUND: In recent years anatomic research has demonstrated the presence of various types of nerve fibre in the cornea. The purpose of this study was to investigate the distribution of catecholaminergic fibres in various corneal layers and to study the effects of an experimental superficial corneal lesion on the pattern of catecholaminergic nerve fibre distribution in the various corneal layers. METHODS: Three weeks after the creation of an alkali burn in the centre of the right cornea of five albino rabbits, the animals were killed, and histologic sections from the cornea of both eyes were stained for observation of catecholaminergic nerve fibres and photographed on black-and-white film. The photographs were examined using the Quantimet image analyser (Leica). RESULTS: Catecholaminergic nerve fibres were observed in the corneal epithelium and the deep stromal layers. Sections from injured cornea showed a drastic reduction in epithelial and superficial stromal catecholaminergic nerve fibres, whereas the nerve fibres in the endothelium and deep stroma were not damaged. INTERPRETATION: Although catecholaminergic nerve fibres were observed in all corneal layers, the pattern of catecholaminergic fibres following the creation of a superficial lesion of the cornea seems to suggest that the superficial and deep nerve fibres may have a different distribution.

Ultrasound biomicroscopy in the clinical evaluation of ab externo holmium:YAG laser sclerostomies.

High-frequency ultrasound biomicroscopy (UBM) has extensive powers of resolution. This makes it possible to explore and study some areas of the anterior segment with a clarity close to that of histologic preparations. High-frequency UBM was used in the clinical evaluation of 10 glaucomatous eyes subjected to ab externo holmium:yttrium-aluminum-garnet (Ho:YAG) laser sclerostomy. The anatomic characteristics of the fistular paths were viewed and compared with echographic images. The authors demonstrated that in the 5 cases where the filtering bleb, fistular path, and internal ostium were present, there was a reduction of intraocular pressure. UBM is a high-definition diagnostic instrument in the follow-up of fistular paths and filtering blebs after Ho:YAG laser sclerostomy, making it possible to reoperate at an early stage before the onset of clinical manifestations.

Age-related macular disease in rural southern Italy.

OBJECTIVE: To report the prevalence of age-related maculopathy (ARM) in Salandra, a small, isolated southern Italian community, to test the hypothesis that an environmental factor, scarce in such a remote community but ubiquitous in modern industrial societies, might modify the risk of developing ARM. DESIGN: Population-based cross-sectional survey. MAIN OUTCOME MEASURES: Prevalence of advanced age-related macular degeneration (ARMD) (geographic atrophy or exudative maculopathy) and ARM (large, soft drusen or retinal pigment epithelium changes, or both) defined by fundus biomicroscopy and 30 degrees stereoscopic, macular photography. Self-sustenance was assessed by interview of participants and local shop retailers. The degree of genetic isolation was computed using a model that fits the genetic population structure with the frequency distribution of surnames in the community. RESULTS: A full ophthalmic examination was undertaken in 366 (63.5%) of 576 eligible participants, 354 (96.7%) of whom had clinical or photographic assessment for the presence of ARMD and 310 (84.6%) of whom had drusen characteristics graded on color transparencies for ARM. The overall prevalence of ARMD was 1.1%. Drusen larger than 50 microns and more numerous than 10 were found in 4.5% of subjects. Salandra was the birthplace of 87.2% of participants and for 77.3% of both parents of each subject. People in the community tended to consume homegrown products. CONCLUSION: The prevalence of ARM may be lower in this self-sustained farming community than elsewhere in the industrialized world.

Work-related accidents of ophthalmologic interest in Italy during 1986-1991.

The authors analysed accidents of ophthalmological interest obtaining information from the database of the INAIL (National Insurance Institute for Professional Casualties) concerning the period of 1986-1991. The INAIL registers all casualties that cause work disabilities exceeding 3 days. The investigation included all job types grouped into two major categories: agriculture (16% of all insured labour) and industry/craftsmanship (84%). Over 78% of the cases examined were in the industry/craftsmanship category. Approximately 22% of the cases were in the agriculture category. Every year in Italy, about 6% of regularly employed workers suffer casualties. The incidence of casualties of ocular interest has been a stable 0.37% in the years examined; 2.88% of these casualties produce permanent consequences (1/10,000 workers per year). The risk in 3 times higher in agriculture.

Structural evidence for membrane lipid changes in human cataract.

Lipid changes in relationship to cataractogenesis were studied with histochemical methods (topoptical reactions) of polarization microscopy. Frozen section of formaldehyde-fixed human lenses were used for these studies. Six lenses were transparent and 14 lenses presented early to confluent cortical opacities. Cell membrane lipids of transparent lenses showed 8.0 +/- 2.7 nm light retardation. In the early cataractous lenses the light retardation of cell membranes was 23.3 +/- 5.0 nm and that of the fusiform and globular lipids was 37.7 +/- 4.0 nm and 48.5 +/- 6.9 mn, respectively. In the non transparent cortical regions of cataractous lenses, membrane lipids were not observed. Similar to other cell membranes, normal lens membranes are composed of loosely organized lipids. In early cataract lipid density uniformly increased along the cell membranes at the clinically transparent areas, while at the areas with clinically evident fine opacities, small fusiform and globuler lipid drops were formed by even more dense lipids. Confluent cortical cataracts were associated with disappearance of membrane lipids. In our study our findings demonstrated intramembrane lipid changes associated with cataractogenesis.

[Parameters for the assessment of inflammation of the anterior segment of the eye]. / Parametri per la valutazione delle flogosi del segmento anteriore dell'occhio.

The authors examine general aspects of the assessment and evaluation of inflammation of the anterior segment of the eye, stressing above all the importance of accurate history taking and correct diagnostic approach. The also define general features of inflammatory processes and analyse the main and most modern instrumental techniques that are essential for precise assessment of clinical parameters of inflammatory conditions of the anterior segment of the eye.

Inorganic element concentrations in cataractous human lenses.

We evaluated the presence of calcium, potassium, zinc, copper, and selenium in human lenses (53 cataractous and 10 clear lenses). The determinations of these elements were done using atomic absorption spectrometry techniques, namely flame and flameless methods, after acidic digestion of the samples. Compared with the results obtained from samples of normal lenses (zinc, 16.5 +/- 2.5 mg/kg dry weight; copper, 0.53 +/- 0.08 mg/kg dry weight; selenium, 0.83 +/- 0.18mg/kg dry weight; potassium, 10,306 +/- 1232mg/kg dry weight, and calcium, 9.9 +/- 2.7mg/kg dry weight), the mean concentration values of the cataractous lenses showed some significant changes. Increases were found for zinc, copper, and calcium; the potassium concentration decreased. No significant changes occurred in selenium values. A positive correlation was found between zinc and copper concentrations (y = 0.030x + 0.007, r = .79). An inverse correlation was evident between calcium and potassium values (y = -0.097x + 1141, r = -.65).

New applications of the neodymium: yttrium aluminum garnet laser in the Q-switched mode: experimental results.

We describe the interaction of the neodymium: yttrium aluminum garnet (Nd:YAG) laser energy with intraocular lenses using the laser in the Q-switched mode. Using this method, it is possible to treat opacities that eventually might occur at the level of the visual axis on the optic faces of polymethylmethacrylate intraocular lenses (IOLs) if safety parameters (perfect focusing, use of additional lenses, and slight and continuous movement of the focal point of the laser) are followed. However, it is not possible to treat the silicone IOLs with the Nd:YAG laser because the threshold values for damage to the IOL are lower than the energy values required for destroying the capsular opacities on the optic axis.

Visual disturbances associated with primary empty sella syndrome in patients with chronic renal failure.

After describing the main clinical features of primary empty sella syndrome and the main hormonal alterations in chronic renal failure, the authors report the results obtained in a group of 33 patients undergoing dialysis three times a week. Each patient had a complete ophthalmologic examination, with electroretinography and visual-evoked potentials, a complete radiologic examination, including skull stratigraphy (particularly of the sellar and parasellar bony structures), and a computed tomographic scan. In the whole group, visual acuity, ocular and lid motility, and visual fields were normal. In two patients, a slight bilateral papilledema, associated with a P100 latency increase and normal morphology and visual-evoked potentials, was reported. Two patients had initial unilateral papillary pallor associated with P100 amplitude alterations. In all four of these patients, radiologic examination showed a markedly pathologic sellar widening with thickening and double contour image of the floor. The report of a primary empty sella was confirmed by computed tomography in all four cases. The authors discuss the possible etiopathogenic mechanisms of the neuroophthalmologic symptoms associated with this syndrome.

Histochemistry and electron-microscopic observation in two cases of granular dystrophy of the cornea.

We report on 2 cases of granular dystrophy (Groenouw type I). We studied the nature and the ultrastructure of the typical stromal deposits by means of histochemical methods and of electron-microscopic examination. These deposits did not stain with Alcian blue, periodic acid-Schiff, Mallory, van Gieson, von Kossa or Congo red so that they are not constituted of proteoglycans, collagen, calcium or amyloid. They probably contain a proteic material. At the electron-microscopic level we observed electron-dense material which was made up of filaments immersed into an amorphous matrix.