Pleomorphic adenocarcinoma of the ciliary epithelium: a clinicopathological, immunohistochemical, ultrastructural, DNA-ploidy and comparative genomic hybridization analysis of an unusual case.

PURPOSE: To describe detailed phenotypic and genotypic analysis of a pleomorphic adenocarcinoma of the ciliary epithelium (CE). CASE REPORT: An 86-year-old white woman developed an enlarging mass protruding from her previously eviscerated left eye 2 months postoperatively. Based on light and ultrastructural microscopy, the final diagnosis was a pleomorphic adenocarcinoma of the ciliary epithelium (CE). DISCUSSION: Cell proliferation indices confirmed the unusually rapid growth rate of this tumor; the peridiploid DNA content might explain the relatively low incidence of distant metastases. An imbalance of the chromosome 6 was also found by Comparative Genomic Hybridization (CGH).

Quality of life in patients with early, moderate and advanced glaucoma.

PURPOSE: To evaluate the quality of life in glaucomatous patients using two different questionnaires: the medical outcomes study 36-item short-form health survey (MOS SF-36) and Viswanathan et al's questionnaire and to compare these two questionnaires. METHODS: Seventy-seven patients with glaucoma were consecutively selected. Two force-choice questionnaires were administered to each patient. Viswanathan et al's questionnaire was related to visual disability and the second was related to the quality of life from the MOS 36-item short-form health survey. Both questionnaires were evaluated among all the considered patients and the results were compared. Then the questionnaire which did the best evaluation was used to test the quality of life in three different subgroups based on the mean deviation of the worse eye. Mann-Whitney non parametric test and Spearman's r coefficient were used and a P value less than 0.05 was considered to be statistically significant. A linear regression model was used. RESULTS: In the entire group (n = 77) the Mean Deviation (MD) was -6.5 +/- 6.8 dB (mean +/- standard deviation) and Corrected Pattern Standard Deviation (CPSD) was 4.7 +/- 4.1 dB. The score of the Viswanathan et al's questionnaire was 8.3 +/- 2.4, while MOS SF-36 score ranged from 60.5% to 100% (mean score %). A significant (P < 0.0001) correlation was found between the score of the Viswanathan et al's questionnaire and MD (r = 0.79), Pattern Standard Deviation (PSD) (r = -0.68) and CPSD (r = -0.61). CONCLUSION: Viswanathan et al's questionnaire was more useful than MOS SF-36, both for the score and for the velocity to use. Furthermore Viswanathan et al's questionnaire was more significantly correlated to visual field MD.

Comparison between relative dispersion analysis of high-pass resolution perimetry and standard threshold perimetry.

PURPOSE: To evaluate the correlation of the dispersion index (DI) of relative dispersion analysis (RDA), a new high-pass resolution perimetry (HRP) index, with other HRP indices and those of the Humphrey standard threshold perimeter (STP) parameters. METHODS: Sixty-eight eyes were randomly recruited. Thirty-one eyes were classified as glaucomatous (high intraocular pressure, abnormal visual field and/or optic disc) and 37 as ocular hypertensives (high intraocular pressure, normal visual field, normal optic disc). All the subjects were examined with Humphrey Perimeter, program 30-2, and HRP. The HRP data were also analysed with the RDA program. Statistical analysis was performed with Student's t-test, Pearson's r correlation coefficient, Mann-Whitney nonparametric test and Spearman correlation coefficient when appropriate. RESULTS: Within the entire sample significant correlations were found between the RDA index (DI) and all the HRP indices (p < 0.001) and corrected pattern standard deviation (p < 0.01), pattern standard deviation (PSD) (p < 0.01), mean deviation (p < 0.05) and short-term fluctuation (p < 0.05) of STP. A stronger correlation was found in glaucomatous patients. In subjects with ocular hypertension DI was only weakly correlated with PSD, local deviation and form index. No difference in DI was found between glaucoma and ocular hypertension. CONCLUSION: The DI of HRP has the theoretical capacity to detect localised inhomogeneity of retinal sensitivity, but at present our data do not support this hypothesis. Before any clinical applications of this index further studies are needed.

Learning effect, short-term fluctuation, and long-term fluctuation in frequency doubling technique.

PURPOSE: To evaluate short-term and long-term fluctuations and learning effects in healthy subjects tested with the frequency doubling technique, which is based on a low spatial frequency and a high temporal frequency stimulus. METHODS: Twenty-three healthy adult subjects were consecutively recruited from volunteers, and 20 subjects finished the study. All the visual fields were assessed by the frequency doubling technique, program C-20, full threshold. The frequency doubling technique presents stimuli on a black-and-white video monitor with specialized control circuitry interfaced to a microprocessor. During program C-20, full threshold, 17 points are tested, one round point centrally and 16 square ones in the periphery up to 20 degrees of eccentricity. Each stimulus consists of a 0.25-cycle/degree sinusoidal grating undergoing a 25-Hz counterphase flicker. One eye of each patient was chosen at random. Each subject was tested once in the first session, three times in the second session, and once in the third and fourth sessions. Both short-term and long-term fluctuation were studied either as the average fluctuation value of all the points tested or as a point-to-point fluctuation. To study the learning effect, the results of the first session were compared with those of the second, the third, and the fourth sessions. RESULTS: The average mean sensitivity of the three examinations of the second session was 30.4 +/- 1.24 dB, and the average short-term fluctuation of all the subjects was 2.16 +/- 0.5 dB. The short-term fluctuation of each point tested ranged from 1.4 to 3.4 dB. The average mean sensitivity for all the sessions was 32.4 +/- 1.14 dB, with an average long-term fluctuation of 3.23 +/- 0.5 dB, and the long-term fluctuation of each tested point ranged from 2.5 to 4.4 dB. A mild learning effect was found between the first section and the others. CONCLUSION: Short-term and long-term fluctuations were similar to those known to occur with the conventional threshold perimetry when they were compared with the literature data. A learning effect was also observed and should be taken into account for the clinical use of this test.

Follicular large-cell lymphoma of the orbit: a clinicopathologic, immunohistochemical and molecular genetic description of one case.

BACKGROUND: Follicular large cell lymphoma of the orbit is a very rare and aggressive lymphoproliferative disease of the ocular adnexa. In this study we analyzed the clinicopathologic characteristics of one patient, including the immunoglobulin gene rearrangement assay by means of polymerase chain reaction. CASE REPORT: A 71-year-old female underwent an incisional biopsy in the superior nasal quadrant of the left orbit following the occurrence of bilateral eyelid edema and ptosis. Histology and immunohistochemistry revealed a follicular large cell lymphoma of the orbit. Computerized tomography aimed at staging the disease revealed a supraclavicular lymphoadenopathy approximately 0.5 cm in diameter. Bone marrow biopsy was negative for lymphoma. The patient was classified as stage IV. She underwent a 10-week cycle of polychemotherapy (VP16, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin). Ten months after therapy, disease recurred at the cervical lymph nodes and the patient underwent a radiotherapy cycle of 4320 cGy with disease remission. At the time of writing, the patient presents a left axillary adenopathy on computerized tomography followup. CONCLUSION: Ophthalmologists should be aware of possible rare occurrences of follicular large cell lymphomas of the orbit. In this case the clinical outcome is always more aggressive than the more common MALT-type lymphoma, which usually exhibits benign behavior.

Correlation between high-pass resolution perimetry and standard threshold perimetry in subjects with glaucoma and ocular hypertension.

PURPOSE: To evaluate the correlation between High-Pass Resolution Perimetry (HRP) and standard threshold perimetry in patients with glaucoma or ocular hypertension. METHODS: 31 glaucomatous patients and 37 ocular hypertension subjects with previous perimetric examination experience were consecutively recruited and only one eye for each patient was selected at random. Glaucomatous patients were classified as having primary open angle glaucoma when they had an abnormal visual field and/or an abnormal optic nerve head (ONH)/retinal nerve fiber layer (RNFL) typical of glaucoma, open angle at gonioscopy and no clinically apparent secondary cause for their glaucoma. Ocular hypertension subjects were defined as having intraocular pressure >21 mm Hg on no treatment, normal visual field, normal ONH and RNFL, elevated intraocular pressure without any treatment. All the subjects were examined with Humphrey Field Analyzer (HFA) 640, 'program central 30-2' (Humphrey Systems, San Leandro, CA, USA) and with High-Pass Resolution Perimeter (HRP), Ophthimus version 2.4,'ring program' (Nikon-HighTech Vision, Goteborg, Sweden). Visual field indices were obtained with both systems: for HFA mean deviation (MD), corrected pattern standard deviation (CPSD) and short term fluctuation (SF), while for HRP global deviation (GD), local deviation (LD), form index (FI) and neural capacity (NC). The data were analyzed by descriptive analysis, Student's t test with Bonferroni's correction or Mann-Whitney non-parametric test and Pearson or Spearman's correlation coefficient. RESULTS: A significant correlation was found between MD and GD (r = -0.81), CPSD and LD (r = 0.87), PSD and LD (r = 0.72). NC was significantly correlated with MD (r = 0.76), GD (r = -0.94). FI was significantly correlated with PSD (r = -0.58), CPSD (r = -0.72), LD (r = -0.56). When the same data were analyzed for the glaucomatous group only, similar results were found; in the ocular hypertensive group no significant correlation was found except between NC and MD (r = 0.52). CONCLUSION: HRP indices vary comparably with HFA indices. Parameters as NC and FI were significantly correlated with standard visual field indices of both HFA and HRP. Although the clinical applications for FI are not clear yet, NC could detect both early glaucomatous damage and age related changes.

Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium.

BACKGROUND: Complete loss of the corneal-limbal epithelium leads to re-epithelialisation by bulbar conjunctival cells. Since conjunctival and corneal-limbal epithelial cells represent two different cell lines, this conjunctival healing of the cornea is followed by stromal scarring, decreased visual acuity, and severe discomfort. Unilateral corneal-limbal epithelial defects can be resolved by the transplantation of limbal grafts taken from the uninjured eye. However, this procedure requires a large limbal graft to be taken from the healthy eye, and is not possible for bilateral lesions. We investigated the possibility of restoring the human corneal surface with autologous corneal epithelial sheets generated by serial cultivation of limbal cells. METHODS: Cells were cultivated from a 1 mm2 biopsy sample taken from the limbus of the healthy eye of two patients with severe alkali burns, and thus complete loss of the corneal-limbal surface, of one eye. Normal corneal differentiation was tested with a specific biochemical marker. Autologous cultured corneal sheets were then grafted onto the damaged eyes of the two patients. The patients were followed up at more than 2 years after grafting. FINDINGS: We have shown that corneal progenitor cells are localised in the limbus, that cultured limbal cells generate cohesive sheets of authentic corneal epithelium, and that autologous cultured corneal epithelium restored the corneal surface of two patients with complete loss of the corneal-limbus epithelium. Long-term follow-up showed the stability of regenerated corneal epithelium and the striking improvement in patients' comfort and visual acuity. INTERPRETATION: The cultivation of corneal epithelium might offer an alternative to patients with unilateral lesions and a therapeutic chance to patients with severe bilateral corneal-limbal epithelial defects. Our findings give a new perspective on the treatment of ocular disorders characterised by stem-cell deficiency.

Evaluation of amblyopic scotoma by electrophysiological examinations and computerized perimetry.

To evaluate amblyopic scotoma and the most affected neural cells in suppressive phenomena, eight patients with deep amblyopia from strabismus (visual acuity of the amblyopic eye between 4/50 and 2/10) underwent a pattern electroretinogram (PERG), pattern visual evoked potential (VEP), and event-related potential (ERP) from visual stimuli, and computerized perimetry. The results of stimulation of the amblyopic eye, the leading eye and the leading eye penalized by Ryser filters were compared statistically. Computerized perimetry was used to quantify the depth and amplitude of the amblyopic scotoma. All electrophysiological potentials were reduced in amplitude and the implicit times of VEP and ERP were longer when stimulating the amblyopic eye compared to the leading eye. Only in PERG the penalization induced major changes. Our data suggest that the important suppressive phenomena present in the squint amblyopic eye involve not only the occipital cortex, but also the cognitive areas.

Argon laser trabeculoplasty: long-term results.

We analyzed the long-term success of argon laser trabeculoplasty (ALT) performed in 237 eyes of 175 patients diagnosed with primary open-angle glaucoma and followed for up to 11 years (maximum, 132 months) after treatment. The cumulative proportion of success, defined as the avoidance of glaucoma surgery or an intraocular pressure never exceeding 22 mm Hg, was calculated throughout follow up using the Kaplan-Meier life-table analysis. The success rates were: 78% at 1 year (n = 205), 71% at 3 years (n = 139), 61% at 5 years (n = 73), and 40% at 10.5 years (n = 19). Our data confirm previous reports of the high initial success rate of ALT, followed by a time-dependent decrease in its efficacy.

Indocyanine green angiographic findings in central serous chorioretinopathy.

The purpose of this study is to better characterise, on the basis of a large number of cases and follow-up evaluations, choroidal abnormalities recently observed with indocyanine green (ICG) angiography in central serous chorioretinopathy (CSC). Digital ICG videoangiography was performed in 145 patients with active or inactive, acute or chronic CSC. Forty-eight patients were re-examined in a follow-up period of 6-22 months (mean 10 months). Areas of choroidal leakage attributable to hyperpermeability of the choriocapillaris were found in 98.6% of patients in association with active or resolved pigment epithelial leaks and pigment epithelial detachments. Diffusion of ICG into the choroid was characterised by rapid centrifugal spreading of the dye with a wash-out pattern which was particularly evident in areas corresponding to pigment epithelial detachments. In patients with a long-standing disease, when choroidal hyperfluorescence faded, hypofluorescent spots became increasingly evident revealing pigment epithelial alterations not shown by fluorescein angiography. Areas of choroidal leakage remained unchanged in each patient during the follow-up period, even when subretinal exudation resolved either spontaneously or after photocoagulation. In 5 eyes we observed the appearance of leakage points on pre-existing areas of choroidal leakage. Zonal hyperpermeability of the choriocapillaris characterises all the evolutional stages of CSC and seems to be the primary alteration of this disease. When it corresponds to pigment epithelial detachments choriocapillaris hypermeability is probably associated with local hyperperfusion.

Study of the correlation between average values of optic disc parameters and their measurement variability using stereovideographic digital analysis.

Purpose of our study was to find whether there is a correlation between average values of optic nerve head parameters and their coefficient of variation for repeated measurements. Disc stereo video images were taken with Topcon Imagenet (IS100) and analyzed with the Optic Disc Analysis program. Eleven normal and 9 glaucomatous eyes were selected. A significant correlation was found for horizontal cup/disc ratio (r = -0.037, p = 0.037) and disc area (r = 0.776, p = 0.027) in intra-observer intra-image repeated measurements. Vertical, horizontal and average cup/disc ratios (r = -0.81, r = -0.74, r = -0.78 p < 0.05) showed a significant correlation for intra-observer inter-image repeated measurements. For inter-observer intra-image measurements, a significant correlation was present for average cup/disc ratio (r = -0.64, p = 0.043). Our data show that bidimensional semiquantitative parameters in use for optic nerve head assessment, analyzed by computerized stereovideography, have an intrinsic measurement variability. The variability is significantly related to the value of the measured parameter only when their reference points are determined manually by the operator.

Deflazacort in the treatment of uveitis: a comparative study versus prednisone.

Since corticosteroids represent a fundamental tool in the treatment of uveitis, we evaluate the clinical efficacy and possible appearance of side effects of deflazacort, a new corticosteroid of third generation, versus prednisone at equiactive dosages. Sixty six patients suffering from recurring acute anterior uveitis (RAAU) and/or chronic anterior uveitis (CAU) were treated with deflazacort or alternatively prednisone in an "open" study. Clinical efficacy, ophthalmological parameters and haemato-bioassays were evaluated on admission and during the treatment period. All patients showed a complete remission of clinical signs and symptoms with both treatment and no statistically significant difference was evidenced between the studied groups. Concerning the possible appearance of side effects, the comparison between deflazacort and prednisone a statistically significant difference. These preliminary results are strongly encouraging and suggest further controlled studies on the employment of deflazacort in the treatment of uveitis.

Photoablative filtration surgery with the excimer laser for primary open-angle glaucoma: a pilot study.

We have performed ab-externo photoablative filtration surgery on 19 patients affected by uncontrolled primary open-angle glaucoma. All cases had wide open angles, were previously treated with argon laser trabeculoplasty and were considered good candidates for trabeculectomy. After topical and peribulbar anesthesia, a limbus-based conjunctival flap was dissected. Photoablation of a rectangular area at the limbus was performed with an argon fluoride excimer laser (193 nm), at 180 mJ x sq cm fluence. The beam was shaped in the appropriate fashion using a custom-made metal mask. Photoablation was continued until aqueous appeared percolating through the juxtacanalicular tissue at the bottom of the crater; a water-tight closure of conjunctiva was then performed. Postoperatively, the anterior chamber reaction was minimal; in no case a flat chamber or choroidal detachment was observed. In 18 of the 19 cases the IOP was significantly lowered, and a filtering bleb developed. Mean preoperative IOP was 26.4 (+/- 7) mmHg. At a median follow-up of 9 months (range 4-15) the IOP is < or = 18 mmHg on no medications in 16 (84%) of the eyes, with a mean value of 13.3 (+/- 6) mmHg. Our short-term results support excimer laser photoablative filtration as a relatively safe and effective procedure for primary open-angle glaucoma.

Fundus angiography with fluorescein-labelled peptide fraction from bovine factor VIII: correlation with histologic findings.

A peptide fraction (VUEFFE) obtained from bovine factor VIII, with a high affinity for vessel endothelium, was bound to fluorescein and used for angiography in rabbits. Several eyes had undergone laser photocoagulation on the retina. The location of the dye was studied histologically with fluorescence microscopy on the enucleated, freeze-dried eyes. The angiographic and histologic findings were compared with findings obtained using sodium fluorescein. Fluorescein-labelled VUEFFE gave a longer lasting fluorescence of the retinal vessels with histologic evidence of dye deposition on the vessel wall. It also showed marked affinity for the photocoagulated tissues, giving intense and prolonged staining of the laser burns. Possible clinical applications are discussed.