Giovanni Calabria

Systemic linoleic and γ-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 &ggr;-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.

LOW SPATIAL-CONTRAST SENSITIVITY IN DRY EYES

PURPOSE Blurred vision in keratoconjunctivitis sicca eyes could be the result of the loss of the glossy surface of the tear film because of changes in composition or thickness irregularities. Spatial-contrast sensitivity in keratoconjunctivitis sicca and normal control eyes was tested before and after a tear substitute. METHODS Three different groups of subjects were enrolled: one group of dry eyes with nonsignificant signs of epithelial disease (n = 12), the second group of dry eye positive with 1% Bengal rose staining of the cornea and of the conjunctiva (n = 18), and a third of normal eyes as control group (n = 15). In all the 45 eyes, spatial-contrast sensitivity was tested under the best correction by means of the Vistech Multivision Contrast Tester 8000 (Vistech Consultants, Dayton, OH, U.S.A.) before and 15 min after the instillation of a 0.4% Na-hyaluronate tear substitute without preservatives. RESULTS A significant decrease of spatial-contrast sensitivity ranging from 35 to 70% was present in keratoconjunctivitis sicca eyes compared with a third group of age-matched normal eyes used as control. The spatial-contrast sensitivity was significantly lower also in the presence of preserved corneal surface. The addition of a tear substitute improved spatial contrast-sensitivity thresholds in all groups. CONCLUSION Tear-film disease can affect the transfer function of modulation of the ocular surface.

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.

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.

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.

Tear mucus crystallization in children with cystic fibrosis.

Cystic fibrosis is characterized by an abnormally high electrolyte concentration in exocrine secretions. The authors performed the tear mucus ferning test in 26 eyes of children with cystic fibrosis and compared the results to those in an equal number of age-matched normals. The results suggest that the increased electrolyte concentration could be responsible for the increased hyperviscosity of mucus. The tear mucus ferning test appears to be a suitable diagnostic test for the assessment of cystic fibrosis.

Retinal pigment epithelial tear following intravitreal injection of bevacizumab (Avastin).

PURPOSE To report one case of retinal pigment epithelium tear following intravitreal bevacizumab injection for neovascular age-related macular degeneration. METHODS A 59-year-old patient presented with occult choroidal neovascularization associated with a serous pigment epithelial detachment secondary to age-related macular degeneration. The patient was treated with an intravitreal injection of bevacizumab. RESULTS The patient developed a retinal pigment epithelium tear 60 days following the intravitreal injection. CONCLUSIONS This report describes the development of retinal pigment epithelium tear after intravitreal bevacizumab injection. Future studies should be performed to evaluate which subtypes of lesions are most susceptible to this potential devastating visual complication.

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.

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.

Pathogenesis of degenerative retinopathies induced by thioridazine and other antipsychotics: a dopamine hypothesis.

Thioridazine and other antipsychotics (neuroleptics, dopaminergic antagonists) can cause degenerative retinopathies with histological, electrophysiological and symptomatological features similar to those of primary retinitis pigmentosa. It was formerly suggested that these retinopathies are due to drug absorption by melanin of the eye which damages the choriocapillaris first and subsequently the photoreceptors and the retinal pigment epithelium. An alternative explanation of the still unclear mechanisms involved in the pathogenesis of thioridazine and other phenothiazines retinopathies has underlined the role of the drug effects on the activity of some retinal enzymatic systems which can lead to retinal dystrophy. More recent data on the complex role of dopamine (DA) and of its receptor subtypes in the retina has provided evidence that the D2 family of DA receptors, in particular the D4 receptor, is involved in the control of the synthesis of melatonin, a factor that has been shown to regulate several aspects of retinal physiology and to increase photoreceptor susceptibility to be damaged by light. Based on this knowledge, as well as on clinical data and on pharmacological considerations concerning the differences recently shown to exist among the various antipsychotics as regards their affinity for the DA receptor subtypes, we hypothesize that neuroleptic induced blockade of retinal D2/D4 receptors is among the initial events of these drug-induced degenerative retinopathies. Clinicians should be aware of the retinotoxic effects not only of thioridazine and some others phenothiazines, but also of those possibly caused by other typical and atypical antipsychotics. By evaluating the retinal status and function before and during the treatment of psychiatric patients, it should be possible to choose more accurately the safest drugs, particularly when treating predisposed subjects.