Loss of chance: a new kind of damage to ophthalmologic patients from Europe to Italy.

This work was inspired by a recent juridical development in Italy, whose purpose is to prevent rejection of damage claims whenever it is not possible to prove a causal link between iatrogenic illicit behavior and damage to the patient, despite the fact that the patient has clearly suffered physical or mental injury. In view of this, some European countries-e.g., France and Germany-have recently come up with a new damage interpretation called loss of chance, i.e., the missed opportunity to get a more favorable outcome through different or more timely and efficient therapies. Although the problem has been thoroughly discussed on several levels, no countries have conformed their legislation accordingly, leaving it up to the courts to settle issues of damage claims where loss of chance can be applied and to resolve doubts about the limits of applicability of this new type of damage interpretation. The concept of loss of chance seems to be applicable to many cases in ophthalmologic practice. For example, glaucoma and macular degeneration are common, serious, and potentially blinding diseases in which delayed diagnosis and therapy reduce the chances not only to limit injuries, but also to stop future progress of the disease. Hence, the authors emphasize that a good practice is the only way for ophthalmologists to avoid malpractice claims related to the new developments in tort law in Italy and in other European countries following the creation of new definitions of damage.

The effect of contour line position on optic nerve head analysis by Heidelberg Retina Tomograph.

PURPOSE: To determine the influence of the contour line position on the Heidelberg Retina Tomograph (HRT) parameters and on the diagnostic capacity of the system. METHODS: Thirty subjects with clinical diagnosis of primary open angle glaucoma and 30 healthy subjects were recruited. For each patient only one eye was randomly chosen. All optic nerve heads (ONH) were analysed with HRT. An operator drew the right contour line in all the considered images, while a second user increased and decreased radius size of 0.05 and 0.1 mm, recalculating each time all the HRT parameters. Five different disc area subgroups were obtained and for each subgroup discriminant formulas were applied. Sensitivity, specificity, and diagnostic precision were considered for each subgroup. RESULTS: Among the HRT parameters, rim area was the most sensitive to the contour line position changes when the radius variation was greater than +/-0.1 mm. For most of the HRT parameters, the differences between subjects with glaucoma and control group did not significantly change when the disc area increased or decreased. Highest diagnostic capacity was observed for Mikelberg and Mardin formulas when the contour line was narrowed, while the cup shape measure value had the best diagnostic capacity when the contour line was larger. CONCLUSIONS: When the disc area was modified, the sensitivity, specificity, and diagnostic capacity of discriminant formulas changed according to the ONH size; however, in the glaucoma clinic, small errors (within +/-0.05 mm) in contour line position did not significantly influence the final HRT diagnostic capacity.

Evidence for aerobic metabolism in retinal rod outer segment disks.

The disks of the vertebrate retinal rod Outer Segment (OS), devoid of mitochondria, are the site of visual transduction, a very energy demanding process. In a previous proteomic study we reported the expression of the respiratory chain complexes I-IV and the oxidative phosphorylation Complex V (F(1)F(0)-ATP synthase) in disks. In the present study, the functional localization of these proteins in disks was investigated by biochemical analyses, oxymetry, membrane potential measurements, and confocal laser scanning microscopy. Disk preparations, isolated by Ficoll flotation, were characterized for purity. An oxygen consumption, stimulated by NADH and Succinate and reverted by rotenone, antimycin A and KCN was measured in disks, either in coupled or uncoupled conditions. Rhodamine-123 fluorescence quenching kinetics showed the existence of a proton potential difference across the disk membranes. Citrate synthase activity was assayed and found enriched in disks with respect to ROS. ATP synthesis by disks (0.7 micromol ATP/min/mg), sensitive to the common mitochondrial ATP synthase inhibitors, would largely account for the rod ATP need in the light. Overall, data indicate that an oxidative phosphorylation occurs in rod OS, which do not contain mitochondria, thank to the presence of ectopically located mitochondrial proteins. These findings may provide important new insight into energy production in outer segments via aerobic metabolism and additional information about protein components in OS disk membranes.

Prospective, multicenter demographic and epidemiological study on vernal keratoconjunctivitis: a glimpse of ocular surface in Italian population.

PURPOSE: To evaluate the frequency and epidemiological features of vernal keratoconjunctivitis (VKC) in Italy. METHODS: a specific electronic clinical chart for vernal keratoconjunctivitis was created to standardize: 1) medical history; 2) diagnostic criteria; 3) signs and symptoms; and 4) treatments. This study involved 6 Italian referral centers for ocular surface diseases: between March 2005 and March 2006, all referred patients were included, clinical data collected and statistically examined. RESULTS: The mean age of the vernal keratoconjunctivitis population (n = 156) was 13.8 +/- 8.8 with 64.1% of subjects under 14 years of age and a male/female ratio of 3.5:1. Among VKC patients, 48.7% showed associated systemic allergic diseases. Only 32.1% of patients were positive for RAST and/or prick test. The limbal form (53.8%) was the most frequent subtype of vernal keratoconjunctivitis. Approximately 9% of patients showed a severe form of vernal keratoconjunctivitis. At the first visit patients were treated with: multiple action or mast cell stabilizer eye drops (58.1% and 41.3% of cases, respectively), topical corticosteroids alone (0.6%) or in association (26.8% of cases). All patients used topical steroids at least once in the studied year. Systemic antihistamine therapy was used by 25.6% of patients. In this cohort, 32.7% of patients required two or more examinations per year for exacerbations of their symptoms. CONCLUSION: Vernal keratoconjunctivitis is a severe ocular condition that mainly affects young males. Vernal keratoconjunctivitis is characterized by different clinical features and therapeutic responses, suggesting the need for a standardized therapeutic approach on the basis of a grading of disease severity.

Comparison between discriminant analysis models and "glaucoma probability score" for the detection of glaucomatous optic nerve head changes.

PURPOSE: The aim of this study was to evaluate and compare 4 different discriminant analysis formulas and the new Glaucoma Probability Score (GPS) for the detection of morphometric optic nerve head changes in chronic open-angle glaucoma. METHODS: This is a prospectively planned cross-sectional study. Two hundred and fourteen consecutive eyes were recruited into this study. For each patient, the eyes were evaluated by a slit lamp examination, and the visual fields were assessed by a Humphrey Field Analyzer 750 (HFA, Humphrey Inc, San Leandro, CA), using the standard full threshold 24-2 (Swedish Interactive Threshold Algorithm) program. The optic nerve heads were morphometrically evaluated using the Heidelberg Retina Tomograph 3 (HRT 3, Heidelberg Engineering, Heidelberg, Germany; software version 3.0). From the HRT data, 4 discriminant analysis formulas and the GPS were considered. All data were analyzed by Student t test and Pearson r coefficient. A linear regression model was also used to determine the independent contribution of variables included in the model. Sensitivity, specificity, diagnostic precision, and receiver operating characteristic curve areas were calculated for all the 5 methods examined. kappa statistic was used to study the agreement among, and between, the 5 different methods. RESULTS: One hundred and nineteen normal eyes and 95 eyes with primary open-angle glaucoma were included in the study. No significant difference was found between the 2 study subgroups in both age and refractive error. Significant (P<0.001) correlations were found between visual field indices and the HRT parameters. Sensitivity, specificity, and diagnostic precision of the 4 formulas ranged between 50% and 99.16%. Bathija et al's formula had the highest diagnostic precision, followed by Mikelberg's formula. Using kappa statistics, kappa ranged from 0.177 to 0.528 when comparing each single discriminant formula with the GPS. CONCLUSIONS: The GPS showed similar sensitivity and specificity to the Mikelberg and Bathija formulas; this method is a promising one for differentiating between healthy and glaucomatous eyes, requiring no subjective user input.

Retinal blood flow autoregulation after dynamic exercise in healthy young subjects.

PURPOSE: To evaluate the retinal blood flow before and after the increase in systemic blood pressure to assess the autoregulation in healthy young subjects. METHODS: Twenty eyes of 20 healthy volunteers were examined. The retinal blood flow was assessed by a Heidelberg retina flowmeter (HRF), while the systemic pressure was assessed by a portable electronic sphygmomanometer. Furthermore intraocular pressure (IOP) was always measured by a Goldmann tonometer immediately after HRF assessments. All measurements of physiological and flow parameters were performed with the subjects seated at rest and then immediately after stair climbing. RESULTS: The IOP decreased significantly after dynamic exercise, while the heart rate and the systemic artery pressure increased significantly. At the baseline, the mean retinal blood flow was 276.8 +/- 80.7 arbitrary units (AU) in the superotemporal area, 243.4 +/- 63.68 AU in the superonasal area, 258.2 +/- 67.37 AU in the inferotemporal area and 243.9 +/- 72.24 AU in the inferonasal area. After dynamic exercise the mean retinal blood flow was 249.8 +/- 86.78 AU in the superotemporal area, 248.7 +/- 63.87 AU in the superonasal area, 245.4 +/- 83.85 AU in the inferotemporal area and 228.8 +/- 62.53 AU in the inferonasal area. No significant change in retinal blood flow was found. CONCLUSION: Our data support the hypothesis that in normal subjects autoregulation is sufficient to compensate the increase in blood pressure and maintain a stable retinal blood flow after exercise.

Comparison between GDx VCC parameter and achromatic perimetry in glaucoma patients.

PURPOSE: To evaluate the correlation between polarimetry parameters and standard threshold perimetry indices. PATIENT AND METHODS: One hundred and eight consecutive glaucomatous patients were recruited in this study. Glaucomatous patients were classified when an abnormal visual field and/or an abnormal optic nerve head were present. One eye was chosen randomly from all the subjects. All optic nerve heads were examined with the GDx variable corneal compensator (VCC) (Laser Diagnostic Technologies, Inc, San Diego, CA) and visual fields were assessed by Humphrey Perimeter, program 24-2, SITA standard (Humphrey Instrument, Inc, San Leandro, CA). GDx VCC parameters and visual field indices were considered. Correlation coefficient was used to compare the 2 sets of data. A linear regression model was also used to calculate the independent contribution of each GDx VCC parameter and to determine which parameter was the most predictive of visual field damage. RESULTS: The mean age (+/-standard deviation) was 61+/-10.3, the average of the mean deviation (MD) was -2.31+/-3.2 dB and the mean pattern standard deviation (PSD) was 3.32+/-2.83 dB. Significant (P<0.05) correlation was found between MD and the nerve fiber indicator (NFI) (r=-0.35), the superior average (r=0.28), the Temporal-Superior Nasal-Inferior Temporal average (r=0.24) and the inferior average (r=0.21). The linear regression model found NFI to be the predictor variable of MD. Significant (P<0.05) correlation was found between PSD and the NFI (r=0.39), the superior and the inferior average (r=0.30), and the Temporal-Superior Nasal-Inferior Temporal average (r=0.29). The linear regression model found NFI to be the predictor variable of PSD. CONCLUSIONS: Some of the GDx VCC indices were significantly correlated to visual field indices in glaucomatous patients, but NFI was the best indicator of visual field damage.

Retinal angiomatous proliferation treated by intravitreal triamcinolone and photodynamic therapy with verteporfin.

PURPOSE: To examine combined treatment of intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP). METHODS: Ten eyes of eight consecutive patients with RAP underwent a single injection (about 20 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity (BCVA) was measured by standardized protocol refraction. RESULTS: Median BCVA was 20/160, 20/64, 20/98, 20/89, 20/89, 20/125 at baseline and 1, 3, 6, 9 and 12 months, respectively. Of ten eyes, six (60%) improved BCVA of at least 3 lines at 1, 3, 6 and 9 months. Four (40%) eyes improved BCVA of at least 3 lines at 12 months. Three eyes (30%) lost >3 lines at 12 months. In all patients intraocular pressure was well controlled. No endophthalmitis, retinal detachment or vitreous haemorrhage developed. CONCLUSIONS: Improvement of BCVA suggests that combination treatment with IVT and PDT for RAP merits further investigation.

Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin.

PURPOSE: To examine combined treatment with intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: In this prospective, interventional case series, 11 eyes of 10 consecutive patients with occult with no classic CNV underwent a single injection (25 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) protocol refraction. RESULTS: Median best-corrected visual acuity was 20/160, 20/80, 20/80, 20/50, and 20/80 at baseline and 1, 3, 6, and 12 months, respectively. Best-corrected visual acuity at baseline was statistically different (P < 0.05) than best-corrected visual acuity at 1, 3, and 6 months. Of 11 eyes, 5 (45.5%), 7 (63.6%), 7 (63.6%), and 4 (36.3%) had improved best-corrected visual acuity of at least 3 ETDRS lines at 1, 3, 6, and 12 months, respectively, while 6 (54.5%), 9 (81.8%), 10 (91%), and 8 (73%) had improved best-corrected visual acuity of at least 2 ETDRS lines at 1, 3, 6, and 12 months, respectively. Two eyes (18%) lost >3 lines at 12 months. One eye had intraocular hypertension at 3 months and was treated with a combination of topical antiglaucomatous drugs. One eye developed a dense cataract at the last follow-up visit. No endophthalmitis, retinal detachment, or vitreous hemorrhage developed. Fluorescein leakage and retinal thickness reduced significantly after treatment. CONCLUSIONS: Improvement of best-corrected visual acuity and lack of fluorescein leakage suggest combination treatment with IVT and PDT for occult with no classic CNV merits further investigation.

Distribution of conjunctival HLA-DR expression and the pathogenesis of damage in early dry eyes.

PURPOSE: To examine the expression of HLA-DR, a marker of inflammation, in the early stages of dry eye disease and to locate the appearance of this marker on specific areas of the bulbar conjunctiva. METHODS: Dry eye patients were identified and their condition classified as mild (n = 16) or moderate (n = 16) based on Schirmer testing, vital staining, tear break-up time, and symptom questionnaire scores. Brush cytology was used to collect epithelial cells from the nasal, temporal, and superior conjunctivae of patients and age-matched controls. HLA-DR positive cells were detected by immunohistochemical staining and quantified. RESULTS: Patients with moderate dry eye had the highest rate of conjunctival HLA-DR-positive cells, with significantly higher rates than controls regardless of which region of the conjunctiva was sampled (P < 0.01). The mild dry eye group had similar rates of HLA-DR-positive cells in the superior conjunctival region compared with controls. However, in the nasal and temporal regions, they displayed a significantly higher rate of HLA-DR-positive cells than controls (P < 0.01) and the nasal region showed a significant difference (P < 0.01) when compared with the temporal one. Some of these mild dry eyes had no vital staining. CONCLUSIONS: The HLA-DR expression pattern in mild and moderate dry eyes appears to reflect disease progression. Overexpression of HLA-DR in mild dry eyes showing no vital staining suggests that inflammation may be a primary cause of ocular surface damage. These data support the use of immunomodulatory drugs in the treatment of dry eye disease.

Correlation between frequency doubling technology and heidelberg retina tomograph.

PURPOSE: To evaluate the association between Heidelberg Retina Tomograph (HRT) parameters and the Frequency Doubling Technology (FDT) indices in ocular hypertension or primary open angle glaucoma patients. METHODS: One eye was randomly chosen from 85 patients with primary open angle glaucoma (abnormal visual field and/or abnormal optic nerve and untreated IOP > 21 mm Hg) and ocular hypertension (normal visual field and normal optic nerve and untreated IOP > 21 mm Hg). All the patients were examined with Humphrey Perimeter program 30-2 full threshold, FDT program C 20-5, and HRT. Findings were analyzed using Pearson's correlation coefficient and linear regression. RESULTS: Within the entire sample of studied subjects we found a statistically significant correlation (Pearson's r) (P < 0.05) between FDT mean deviation and RA, CA, RV, CSM, RNFLt, and RNFLc of HRT, and between FDT pattern standard deviation and RA, CA, VOLC, CV, RV, CSM, RNFLt, and RNFLc of HRT. Linear regression analysis showed that cup shape measure was the most predictive parameter for FDT MD. No correlation was found between HRT parameters and FDT PSD indices in the glaucoma subgroup; in the ocular hypertensive subgroup some correlation was found between FDT PSD and some of the HRT parameters. CONCLUSION: In the entire group, cup shape measure showed to be the most significant factor correlating functional and morphologic changes. The presence of significant correlations between some HRT parameters and visual field indices in the ocular hypertensive and glaucoma subgroup suggested that HRT parameters and FDT indices could detect glaucoma damage differently.

Effects of a 0.9% sodium chloride ophthalmic solution on the ocular surface of symptomatic contact lens wearers.

BACKGROUND: Ocular surface-related discomfort is the main reason for stopping contact lens wear. We carried out a study to evaluate the efficacy of preservative-free artificial tears containing 0.9% sodium chloride on ocular surface signs and symptoms in contact lens wearers experiencing discomfort and its possible influence on the duration of contact lens wear. METHODS: We studied 49 contact lens wearers experiencing discomfort who had normal results of slit-lamp biomicroscopy, a fluorescein tear film break-up time (BUT) of 10 seconds or more, and wetting greater than 5 mm in 5 minutes on the Schirmer 1 test with and without anesthesia. Twenty-nine subjects (16 men and 13 women with a mean age of 32.5 years [standard deviation (SD) 8.7 years]) received one instillation of the 0.9% sodium chloride solution four times daily in the lower conjunctival fornix for 21 days. Twenty subjects (12 men and 8 women with a mean age of 35.1 [SD 6.2] years) received no drops and served as a control group. The overall comfort and duration of contact lens wear, results of tear film analysis and adverse events were recorded on days 7 and 21. Patients rated their symptoms (while not receiving any medications or hydrating solutions) on a 100-mm visual analogue scale with "Excellent (lenses not felt)" at the left and "Very uncomfortable (lenses cause irritation or discomfort)" at the right. Measurement of corrected visual acuity, slit-lamp examination, determination of the tear film BUT, the Schirmer 1 test with and without anesthesia, and assessment of the colour and surface of the lens were performed at baseline and at day 21. We analysed the data for the more uncomfortable eye or, if the eyes were equally uncomfortable, the right eye. RESULTS: Significant lessening of ocular discomfort was observed in the treatment group during the study: the mean rating on the visual analogue scale at baseline was 60.2 mm (SD 12.7 mm), compared with 35.8 mm (SD 18.0 mm) at day 21 (p < 0.001, Student's t test). The duration of contact lens wear was significantly longer at day 21 than at baseline (7.0 [SD 2.6] hours vs. 6.4 [SD 2.6] hours, p < 0.05, Student's t test), and the proportion of subjects with conjunctival hyperemia was significantly lower at day 21 (48.3% vs. 82.8%, p < 0.05, chi2 test). No statistically significant changes were observed in tear film BUT, results of the Schirmer 1 test, corneal punctate staining by fluorescein or results of tear film analysis. The treatment was well tolerated by all patients. No significant differences in any of the variables studied were observed in the control group. INTERPRETATION: Treatment with a preservative-free 0.9% sodium chloride ophthalmic solution reduced ocular surface discomfort and extended the duration of contact lens wear without interfering with the tear film or contact lens materials. Long-term studies are needed to confirm the role of this solution in reducing discomfort experienced by contact lens wearers.

Retinal peripapillary blood flow before and after topical brinzolamide.

PURPOSE: To study the effect of topical brinzolamide on retinal capillary blood flow by the Heidelberg Retina Flowmeter (HRF) in patients with glaucoma. METHODS: Twenty patients with glaucoma were consecutively recruited. One eye for each patient was randomly selected. Patients were classified as glaucomatous if they had an abnormal visual field and/or an abnormal optic nerve head with an intraocular pressure (IOP) greater than 21 mm Hg without any treatment. After an eye examination, baseline retinal blood flow measurements were made with confocal scanning laser Doppler flowmetry. Blood flow and IOP measurements were then repeated after 1 month of treatment. Blood flow measurements were analyzed by using an automatic full-field perfusion image analysis (AFFPIA) program. The blood flow was calculated in the superior and inferior part of the optic disk. In each area, the blood flow was calculated as temporal area, the nasal area and the rim area as for software AFFPIA. RESULTS: The mean age of the patients was 56 +/- 7 (mean +/- standard deviation) years. The mean IOP before treatment was 23.7 +/- 1.5 mm Hg while the mean IOP after 4 weeks of treatment was 19.1 +/- 2.2 mm Hg. This difference was statistically significant (p < 0.01). Significant (p < 0.05) increases in retinal blood flow were found for the temporal and nasal areas between baseline and 1 month after the treatment. No difference was found between superior and inferior sectors. CONCLUSION: Topical brinzolamide reduced the IOP significantly and apparently improved retinal blood flow as measured by the HRF.

Short-term effects of bimatoprost in glaucoma patients from an outpatient clinic.

PURPOSE: A drug utilization trial was performed to investigate acute versus short-term effects after switching or adding bimatoprost in open-angle glaucoma patients over a 3- month observation period. METHODS: One (1) eye was randomly chosen from 47 glaucomatous patients (abnormal visual field and/or abnormal optic nerve and intraocular pressure (IOP) above 21 mmHg without treatment). Only patients who did not reach the target IOP with their ongoing treatment were recruited in this study. IOP was measured at baseline, after 1 hour, and 2 hours from the first instillation and after 1 week, 1, and 3 months of treatment. RESULTS: The IOP before bimatoprost administration was 20.16+/-3.6 mmHg (mean+/-standard deviation). There was no statistically significant decrease of IOP after 1 hour (mean IOP, 19.96+/-4.25 mmHg) and after 2 hours (mean IOP, 17.73+/-3.24 mmHg). Statistically significant (p<0.001) decreases after 1 week (mean IOP, 16.48+/-2.9 mmHg), after 1 month (mean IOP, 16.48+/-2.9 mmHg) and after 3 months (mean IOP, 16.15+/-2.7 mmHg) were found. CONCLUSION: The results suggested that bimatroprost had a significant acute effect on IOP in monotherapy, while no significant effect was found when the therapy was switched or added. The effect for primary open-angle glaucoma was very evident. There was no specific side effect attributable to combining bimatoprost with any of the treatments in use.

Role of amniotic membrane transplantation for conjunctival reconstruction in ocular-cicatricial pemphigoid.

PURPOSE: To evaluate the role and the effectiveness over time of amniotic membrane transplantation (AMT) as a first-step procedure to treat conjunctival reconstruction in late-stage ocular-cicatricial pemphigoid (OCP). DESIGN: Prospective interventional noncomparative case series. PARTICIPANTS: Nine eyes (9 patients) with advanced OCP. METHODS: Preoperatively, the ocular surface conditions were evaluated by immunohistochemistry of conjunctival biopsy and impression cytology specimens. The amniotic membrane was obtained during cesarean section from women who were 39 weeks pregnant and seronegative for human immunodeficiency virus, hepatitis B and C, and syphilis; it was processed, histologically tested, and stored at -80 degrees C. After scar tissue was removed, the preserved amniotic membrane was placed over the cornea, the bulbar, and tarsal conjunctiva, and was secured with 8-0 Vicryl sutures to the conjunctival edges and the deep fornices with double-armed 6-0 silk sutures. In 2 cases a double layer of amniotic membrane was transplanted. All patients received immunosuppressive systemic therapy and preservative-free tear substitutes and steroids topically for at least 6 months. During follow-up (average, 48 weeks; range, 28-96 weeks), a new standardized method was used to evaluate the fornix depth, and impression cytology testing was performed and conjunctival inflammation recorded and used as parameters for monitoring disease activity. MAIN OUTCOME MEASURES: Symblepharon, increased inferior fornix depth, presence of conjunctival goblet cells, and the degree of conjunctival inflammation. RESULTS: The conjunctival surface was free from symblepharon in all subjects for the first 16 weeks. At the week 28 examination, a small area of symblepharon was present in four eyes (44.4%). The depth of the fornix was significantly (P < 0.0001, analysis of variance) improved at weeks 4, 16, and 28. The normal conjunctival epithelium with goblet cells was restored in 6 of 9 eyes (66.7%) at the week 4 examination and in 4 eyes (44.4%) at the week 28 examination. Conjunctival inflammation was clinically but not statistically reduced. The visual acuity improved in 5 subjects. CONCLUSIONS: AMT can be a first-step procedure for ocular surface reconstruction in OCP, but its effectiveness deteriorates slightly over time.

Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component.

PURPOSE: To evaluate the efficacy and anti-inflammatory activity of systemic linoleic (LA) and gamma-linolenic acid (GLA), which decrease chronic inflammation in rheumatoid arthritis, on the ocular surface of patients with keratoconjunctivitis sicca. METHODS: In a randomized clinical trial, 26 patients with aqueous-deficient keratoconjunctivitis sicca were consecutively selected from patients presenting to Department of Neurosciences, Ophthalmology and Genetics, University of Genoa. The diagnosis was based on dry eye symptom survey score, Schirmer-1 test values, positive vital staining with lissamine green, and fluorescein break-up time (FBUT). All patients had ocular surface inflammation based on HLA-DR expression, a major histocompatibility class II antigen, on epithelial bulbar conjunctiva samples. The subjects were randomly divided into two groups of 13 patients each. The study group received tablets containing LA (28.5 mg) and GLA (15 mg) twice daily for 45 days and used tears; the control group received a tear substitute and a placebo tablet for 45 days. RESULTS: Statistically significant changes in symptoms (p < 0.005), lissamine green staining (p < 0.005), and ocular surface inflammation (p < 0.05) occurred in the study group compared with controls. HLA-DR expression varied from 58.5 +/- 14.1% positive conjunctival cells to 41.3 +/- 18.9% in the treated group and from 61.4 +/- 21.9% to 58.0 +/- 13.3% in the controls. No statistically significant difference between groups was found for FBUT and the Schirmer-1 test. CONCLUSIONS: Therapy with LA and GLA and tear substitutes reduces ocular surface inflammation and improves dry eye symptoms. Long-term studies are needed to confirm the role of this new therapy for keratoconjunctivitis sicca.

Detection of glaucomatous visual field defect by nonconventional perimetry.

PURPOSE: To report the correlations among Humphrey Field Analyzer 750 (HFA), high-pass resolution perimetry (HRP), and frequency-doubling technology (FDT) perimetry in glaucoma patients and ocular hypertensive patients. DESIGN: Cross-sectional study. METHODS: Eighty-two eyes of 82 consecutive patients with primary open-angle glaucoma (POAG) or ocular hypertension were included in this study. One eye of each patient was randomly selected for data analysis. Visual fields were assessed by HFA, HRP, and FDT perimetry. HRP global deviation (HRP-GD), HRP local deviation (HRP-LD), FDT-mean deviation (FDT-MD), and FDT-pattern standard deviation (FDT-PSD) were considered for the analysis. Clinical agreement between HRP and FDT was evaluated. All data were analyzed by Pearson r coefficient when the distribution of the data was normal and by Spearman coefficient correlation when the distribution of the data was not normal. A P <.05 was considered statistically significant. RESULTS: Fifty-two eyes (52 patients) were classified as glaucoma and 30 eyes (30 patients) as ocular hypertension. In the entire group, a significant (P >.001) correlation was found between the HFA indices and those of either HRP or FDT. A significant (P <.001) correlation was found between HRP-GD and FDT-MD as well as between HRP-LD and FDT-PSD. In 14% of the glaucomatous patients and in 33% of the subjects with ocular hypertension, FDT and HRP showed different clinical features. CONCLUSIONS: Our data suggest that FDT and HRP are useful for detection of early glaucomatous visual field damage.

Intraobserver reproducibility of a two-dimensional mapping of the optic nerve head perfusion.

PURPOSE: To evaluate the intraobserver reproducibility of a software designed to assess retinal blood flow with the Heidelberg Retina Flowmeter (HRF). METHODS: Ten subjects were consecutively recruited, and one eye of each patient was randomly selected for study. Blood flow measurements were analyzed by using an automatic full field perfusion image analysis (AFFPIA) program, which calculates the Doppler frequency shift and hemodynamic variables (flow, volume, and velocity) for each pixel. The resulting perfusion image is processed with respect to underexposed and overexposed pixels, saccades, and retinal vessel tree. Intraobserver reproducibility was calculated for the AFFPIA program. All the optic nerve heads were horizontally divided into three sections (superior, central, and inferior). The retinal blood flow was calculated in the superior and inferior section, and each section was further divided into three areas (temporal, nasal, and rim). The blood flow was evaluated for each area. RESULTS: When the same observer analyzed the same image five times (intraobserver intraimage reproducibility), the AFFPIA coefficient of variation ranged from 0.5% to 5% in the temporal area, from 0.1% to 5.3% in the nasal area, and from 0.5 to 28% in the rim area. When the same observer analyzed three different images of the same section once (intraobserver interimage reproducibility), the AFFPIA coefficient of variation of flow measurements ranged from 1% to 7.3% in the temporal area, from 1.5% to 10% in the nasal area, and from 2 to 30% in the rim area. CONCLUSION: Retinal blood flow measured by HRF and analyzed by AFFPIA had good intraobserver reproducibility. The reproducibility was significantly better in the temporal and nasal areas than in the rim area.