Michela Fresina

Ocular surface changes over the menstrual cycle in women with and without dry eye

Aim. To analyze whether dry eye symptoms and ocular surface parameters change during different phases of the menstrual cycle. Method. Twenty-nine women of fertile age and with regular, 26–29-day menstrual cycles were included in the study. Fourteen subjects suffered and 15 did not suffer from dry eye symptoms. Symptoms were scored by the validated Ocular Surface Disease Index questionnaire. Tear production was evaluated with the Schirmer I test and the Schirmer II test (Jones test); tear stability with tear breakup time and Ferning test; and degree of dryness by the tear function index and imprint conjunctival cytology. Degree of inflammation was evaluated with conjunctival brush cytology and concentration of exudated serum albumin in tears. Hormonal cytology procedures were applied to exfoliated cells in tears. Patients were analyzed during menstruation, in the follicular phase and the luteal phase over two consecutive cycles, and results were statistically evaluated. Results. Subjective symptoms, tear production and stability, surface dryness and inflammation were significantly related to hormonal fluctuations in the menstrual cycle. In particular, the impairment of these functions appeared to be related to the estrogen peak occurring during the follicular phase, especially in patients with dry eye. Conclusion. The ocular surface is confirmed to be an estrogen-dependent unit; clinicians should take into account these cyclic variations during examination of subjects affected by symptoms of eye dryness.

Electrophysiological detection of delayed postretinal neural conduction in human amblyopia.

PURPOSE To evaluate macular function and neural conduction along postretinal visual pathways in amblyopic patients. METHODS Twenty-five anisometropic amblyopic patients (mean age, 7 ± 1.9 years; visual acuity [VA]: 0.44 ± 0.27 logMAR in amblyopic [AM] eyes and 0.023 ± 0.067 logMAR in sound [SE] eyes) and 25 age-similar control subject ([CE] eyes, VA of 0.0 ± 0.0 logMAR in both eyes) were enrolled. In AM, SE, and CE eyes, simultaneous pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded in response to checks reversed at the rate of two reversals/second stimulating macular or extramacular areas (the check edge subtended 15 minutes and 60 minutes of visual arc, respectively). RESULTS Nonsignificant differences (ANOVA, P > 0.005) were observed in PERG, in VEP responses to the 60-minute stimulus, and in retinocortical time with the 60-minute stimulus (RCT; the difference between VEP P100 and PERG P50 implicit times) between AM, SE, and CE eyes. AM eyes showed a significant (P < 0.005) increase in VEP P100 implicit time and in RCT in response to the 15-minute stimulus, compared with the values observed in SE and CE eyes. In AM patients, the interocular difference in VA was significantly (Pearsons test, P < 0.005) related to the interocular difference VEP P100 latencies and RCT with the 15-minute stimulus. CONCLUSIONS Amblyopic eyes showed abnormal visual cortical responses only when the macular area was stimulated (increase in VEP P100 implicit times with the 15-minute stimulus). This functional impairment, in the presence of normal macular function (PERG responses similar to control eyes) may be attributable to a delay in postretinal neural conduction (increase in RCT).

Medical Treatment of Amblyopia: Present State and Perspectives

A brief review is provided on the role of experimental modulation of the visual system during its plastic period. The importance of several substances has been demonstrated. Potential clinical applications of available studies on the treatment of amblyopia are summarized. The role of the dopaminergic system and particularly of dopamine in amblyopia are also discussed. The results of the use of cytidine-5′-diphosphocholine (citicoline) in amblyopia are evaluated in detail. The advantages of and indications for an association of citicoline with part-time occlusion are also discussed. Finally, new administration modalities of citicoline, more detailed evaluation of its efficacy, and the use of new substances are briefly analyzed.

A Novel Scraping Cytology Score System (SCSS) Grades Inflammation in Dry Eye Patients

Purpose: We propose a conjunctival Scraping Cytology Scoring System (SCSS) as a reliable method to diagnose and score ocular surface inflammation in dry eye. Methods: Twenty normal subjects and 46 patients with dry eye of various severities were included in the study. Clinical signs were scored 1–4; an Ocular Surface Disease Index (OSDI) questionnaire was used to grade subjective symptoms. Concentrations of serum albumin and interleukin-6 (IL-6) in tears were evaluated. Scraped conjunctival cytology samples were processed and examined with light microscopy. The number of inflammatory cells was staged and sub-scores were assigned. SCSS resulted from their sum and ranged from 0–12. Statistical evaluation was performed by applying the unpaired Students t-test and the Spearmans correlation test (significance p < 0.05). SCSS was also analyzed for sensitivity, specificity, ROC curves, likelihood ratio LR+, positive (PPV) predictive value. Results: SCSS was positively correlated to clinical sign score, OSDI score, exudated serum albumin, and IL-6 in either control (Spearmans correlation test always p < 0.05) and in dry eye patients (respectively, p < 0.0001, p < 0.01, p < 0.05, and p < 0.0001). SCSS ≥ 4 was selected as the cut-off value for moderate dry eye (LR+ 10,9; PPV 22,5), SCSS ≥ 9 was selected as the cut-off value for severe dry eye (LR+ 15,6; PPV 26,2). Conclusions: SCSS can be applied in any trained laboratory. It is correlated with clinical signs and symptoms, and it shows a diagnostic performance to grade inflammation in dry eye, comparable to more expensive cytokine assay.

Subjective Discomfort Symptoms Are Related to Low Corneal Temperature in Patients With Evaporative Dry Eye.

Purpose: To measure the corneal temperature in patients with dry eye (DE) and to correlate the values with subjective discomfort symptoms. Methods: Twenty-four patients with DE (scored as DEWS severity grade 2 to 3) and 15 age-matched normal control subjects were enrolled. Subjective symptoms of discomfort were scored with an Ocular Surface Disease Index questionnaire, and a 100-mm horizontal visual analog scale (VAS) technique was used to measure symptom intensity. Schirmer I test, tear film breakup time (TFBUT), and Oxford grade scoring were performed in all subjects. Dynamic infrared noncontact thermal imaging (Tomey TG 1000) was used to measure the central corneal temperature (CCT). After training, subjects were asked to maintain their eyes forcedly open and to signal the discomfort onset time (DOT). The temperature was measured at eye opening (T0) and every second during 10 seconds of sustained eye opening (T10). The first discomfort sensation onset time (DOT) was also recorded. Temperature values were correlated with the clinical tests, Ocular Surface Disease Index, VAS, and DOT, and data were statistically evaluated (significance P < 0.05). Results: The corneal temperature immediately after eye opening was significantly lower in patients with DE than in controls, in correlation to the subject age, VAS, and TFBUT. A 3-phase cooling profile in patients with DE and a point of highest decrease (HD) in both groups were identified. DOT occurred earlier in patients with DE than in controls (5.9 vs. 15.9 seconds) and was strongly correlated to the VAS, TFBUT, and CCT-HD. Conclusions: Subjective sensation of discomfort occurred earlier in patients with DE than in controls, in correlation to low corneal temperatures and enhanced tear evaporation.

Corneoscleral limbus in glaucoma patients: in vivo confocal microscopy and immunocytological study.

PURPOSE To investigate morphologic changes of the corneoscleral limbus in glaucoma patients using laser scanning confocal microscopy (LSCM) and impression cytology (IC). METHODS Eighty patients with glaucoma and 20 with dry eye were enrolled; 20 healthy subjects served as controls. Patients underwent the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time, corneal staining, Schirmer test I, and LSCM of the limbus. Laser scanning confocal microscopy evaluated the limbal transition epithelium (LTE) regularity, dendritic cell (DC) density, and palisades of Vogt (POV). Impression cytology was performed and samples stained with HLA-DR and IL6. RESULTS Glaucomatous patients were divided into three groups: Group 1 (40 eyes): one drug; Group 2 (20): two drugs; and Group 3 (20): three or more drugs. Limbal transition epithelium regularity was worse, and DC density higher in Groups 2, 3, and dry eyes compared with Group 1 and controls (P < 0.01). Preserved drugs worsened LTE regularity and induced higher DC density compared with preservative-free (PF) drugs (P = 0.041; P = 0.004). Despite typical POV architecture was preserved, signs of inflammation were found in glaucoma groups. HLA-DR and IL-6 positivity were higher in Groups 2, 3, and dry eye compared with controls (P < 0.001), and in preserved versus PF drugs (P < 0.05; P < 0.001). Dendritic cell density and LTE regularity correlated with HLA-DR, IL-6, and OSDI score in glaucoma groups and dry eyes (P < 0.001). CONCLUSIONS Laser scanning confocal microscopy and IC documented antiglaucoma therapy induced morphologic alterations of limbus, which may play a role in the glaucoma-related ocular surface disease. Further studies are required to determine if limbal changes affect stem cell viability.

Dry Eye Disease Is Already Present in Hematological Patients Before Hematopoietic Stem Cell Transplantation.

Purpose: To analyze ocular surface parameters in patients before hematopoietic stem cell transplantation (HSCT) and to correlate them with hematological characteristics. Methods: This is a retrospective analysis of prospectively collected data from 203 patients undergoing HSCT. Demographic data and hematological parameters (disorder type and stage) were collected from clinical charts. Ocular surface parameters (ocular surface disease index; Schirmer test I; tear film break-up time; corneal esthesiometry; and corneal and conjunctival staining) were analyzed the day before beginning the conditioning treatment for HSCT preparation. Results: A high prevalence of dry eye (DE) was found: 116 patients (57.2%) were diagnosed as not suffering from DE, whereas 87 patients (42.8%) were diagnosed as having DE. Of these, 26 were classified as dry eye workshot (DEWS) severity score 1, 46 as DEWS score 2, and 15 as DEWS score 3. Tear film break-up time was found to be the only parameter statistically worse in the chronic lymphoproliferative disorder group compared with the stem cell malignancy group. Older age [odds ratio (OR) 1.03], female sex (OR 2.03), advanced stage of hematological disease (OR 1.4), and previous auto- or allo-HSCT (OR 1.9) showed a significant positive association in predicting DE onset before transplantation. Conclusions: DE was already present in a significant number of patients suffering from hematological disease before HSCT. Some hematological parameters seemed to influence this percentage. These results highlight the role of ocular surface examination by an ophthalmologist in hematological patients before HSCT, with the aim of diagnosing and, if necessary, treating DE patients early.

Targeting growth factor supply in keratopathy treatment: comparison between maternal peripheral blood and cord blood as sources for the preparation of topical eye drops

BACKGROUND Epitheliotrophic growth factors (GF) can be supplied topically to patients with severe keratopathy through a variety of blood-derived products. We compared GF content in adult peripheral blood serum (PB-S) and cord blood serum (CB-S) as potential sources of GF. To limit inter-individual variability the assessment was performed in maternal-child pairs at the time of delivery. MATERIAL AND METHODS The amounts of epidermal GF (EGF), insulin-like GF (IGF), transforming GF-beta (TGF-β), vascular endothelial GF (VEGF) in CB units collected from the umbilical vein and PB from mothers (each group n=30) were estimated by enzyme-linked immunosorbent assays. Obstetric characteristics and haematological data were recorded from the archives of the Emilia Romagna Cord Blood Bank. Statistical evaluations were performed by Wilcoxons test and correlations between variables were determined using Spearmans (ρ) coefficient; p-values <0.05 were considered statistically significant. RESULTS EGF, TGF-β and VEGF levels were significantly higher in CB-S than in PB-S (median 1,254.4 vs 646.0 pg/mL, 51.3 vs 38.4 μg/mL and 686.8 vs 30 pg/mL, respectively; all p<0.0001) whereas IGF content was significantly higher in PB-S than in CB-S (159.9 vs 53.5 pg/mL, respectively; p<0.0001). In CB-S, the CD34(+) cell concentration appeared to be related to EGF, IGF and TGF-β levels whereas white blood cell count appeared to be related to EGF and TGF-β levels. VEGF levels showed no relation to the haematological parameters considered. Platelet counts were not related to GF level in either CB or PB. DISCUSSION The GF content in the two blood sources was different, with CB containing larger amounts. Each GF selectively regulates cellular processes involved in corneal healing, so the use of PB or CB should be targeted to supply specific GF on the basis of the type and severity of the keratopathy.

ET-1 Plasma Levels, Aqueous Flare, and Choroidal Thickness in Patients with Retinitis Pigmentosa.

Purpose. To assess endothelin-1 (ET-1) plasma levels, choroidal thickness, and aqueous flare in patients with early stage retinitis pigmentosa (RP) and to search for possible correlations. Methods. We compared 24 RP patients with 24 healthy controls. Choroidal thickness and aqueous flare were measured, respectively, by using a spectral domain optical coherence tomography and a laser flare-cell meter, whereas plasma samples were obtained from each patient to evaluate ET-1 plasma levels. Results. Notably, RP subjects showed significantly increased ET-1 plasma levels and reduced choroidal thickness compared with controls: 2.143 ± 0.258 versus 1.219 ± 0.236 pg/mL, P < 0.002, and 226.75 ± 76.37 versus 303.9 ± 39.87 μm, P < 0.03, respectively. Higher aqueous flare values were also demonstrated in RP compared to controls: in detail, 10.51 ± 3.97 versus 5.66 ± 1.29 photon counts/ms, P < 0.0001. Spearmans correlation test highlighted that the increase of ET-1 plasma levels was related with the decrease of choroidal thickness (r = −0.702; P < 0.023) and the increase of aqueous flare (r = 0.580; P < 0.007). Conclusions. Early stage RP patients show a breakdown of blood-ocular barrier and increased ET-1 plasma levels and these findings may contribute to the reduction of choroidal thickness.

Discomfort symptoms reduction and ocular surface parameters recovery with Artelac Rebalance treatment in mild-moderate dry eye.

Purpose To evaluate Artelac Rebalance® eyedrops’ efficacy in symptoms reduction, ocular surface parameters recovery, and tolerability in the treatment of mild to moderate dry eye. Methods Fifteen patients were enrolled. Inclusion criteria were Ocular Surface Disease Index (OSDI) score >16, tear film break-up time (TFBUT) <10 seconds, Schirmer test I >10 mm/5 min, and mild ocular surface damage (Oxford grading) ≤3. Artelac Rebalance® eyedrops were administered 3 times daily for 2 months. Patients were evaluated at enrollment, after 2 days of washout (baseline), and after 1 and 2 months of treatment. Parameters for ocular discomfort (OSDI score), tear film quality (Schirmer test I, TFBUT, tear osmolarity), ocular surface damage (fluorescein staining, conjunctival imprint cytology), and inflammation (scraping cytology and exuded serum albumin) were measured. Tolerability and satisfaction were assessed by validated questionnaires. Results At endpoint versus baseline, all variables showed a statistically significant improvement (paired Student t test, p<0.01 for all parameters) as follows: OSDI score (21.9 ± 10.6 vs 35.8 ± 12.2), TFBUT (6.5 ± 1.1 s vs 5.2 ± 2.3 s), Oxford grading of corneal and conjunctival damage (0.56 ± 0.50 vs 1.16 ± 0.37), tear osmolarity (294.6 ± 2.1 mOsm/L vs 303.1 ± 4.6 mOsm/L), conjunctival goblet cell density/mm2 (140.8 ± 43.3 cells/mm2 vs 115.1 ± 15.8 cells/mm2), scraping cytology score (2.9 ± 1.0 vs 4.2 ± 1.3), and percentage of serum albumin in tears (9.2% ± 4.8% vs 24.1% ± 10.8%). Tolerability and satisfaction were scored high, with no adverse events reported. Conclusions Application of Artelac Rebalance® eyedrops for 2 months in mild to moderate dry eye resulted in a reduction of ocular inflammation parameters, ocular surface damage, and subjective discomfort symptoms, with a parallel improvement in tear film quality (measured by TFBUT and osmolarity).