Measurement of health‐related quality of life with glaucoma: validation of the Glau‐QoL© 36‐item questionnaire

Purpose: To validate a glaucoma‐specific health‐related quality of life (HRQoL) questionnaire: the Glau‐QoL^©. Methods: Patients with ocular hypertension (OHT) or glaucoma took part in a cross‐sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36‐item Glau‐QoL^©, designed from in‐depth patient interviews. Results: The clinical validity of the Glau‐QoL^© was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self‐image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self‐image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau‐QoL^©, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) ≥ 0.69. Internal consistency reliability was high (Cronbach's α coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self‐image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain. Conclusions: The Glau‐QoL^© questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT.     

Consensus on neovascular glaucoma

Neovascular glaucoma is a dreadful pathology with a rapid spontaneous evolution responsible for painful and blind eye. The main cause is an anterior neovascular proliferation following a broad retinal ischemia. Early diagnosis and treatment are required in order to maintain a good visual status and a satisfactory IOP control with medical, surgical or cylodestructive procedures. In any case, the treatment of the retinal ischemia has to be performed. One must keep in mind that the most efficient way to avoid the incidence of neovascular glaucoma is a strict control of clinical situations potentially responsible for retinal ischemia, namely VRO in elderly patients and diabetic retinopathy in younger patients.     

Toxicity of preserved and unpreserved beta-blocker eyedrops in an in vitro model of human conjunctival cells

PURPOSE: To compare the toxicity of a short-time application of timolol with benzalkonium chloride (timolol-BAC+) and unpreserved timolol (timolol-BAC-) in an in vitro model of human conjunctival cells. METHODS: Chang's conjunctival cell line (ATCC CCL 20.2) was treated for 15min. with 0.1%, 0.25% or 0.4% timolol-BAC(+) or BAC(-) and then examined immediately or 24h later. Cell viability, chromatin condensation, mitochondrial mass and activity, free radicals production were studied by microplate cold light cytometry. Moreover, relative cell number was evaluated by crystal violet colorimetric test. In addition, cell size and the expression of an apoptotic marker Apo2.7 were studied by flow cytometry. RESULTS: Timolol-BAC(+) induced a rapid decrease in cell viability ranging from 40% immediately after treatment to 85% 24h later. A small, significantly less important decrease in cell viability was also observed with all tested concentrations of timolol-BAC(-). 24h after treatment with 0.25% timolol-BAC(+), the relative cell number was reduced by 55% whereas it did not vary after 0.25% timolol -BAC(-) treatment. Only timolol-BAC(+) induced chromatin condensation, decrease in mitochondrial membrane potential and cell size reduction. Moreover, cells treated with timolol-BAC(+) overexpressed the apoptotic marker Apo2.7. Also reactive oxygen species (ROS) production was significantly more important after cell exposure to timolol-BAC(+). CONCLUSION: In our model of conjunctival cells in vitro, timolol-BAC(+) induced irreversible cytotoxic damage with some characteristics of apoptosis. The active compound of timolol-BAC(-) could be responsible for ROS production and for cell viability variations. Oxidative stress could also play a role in timolol-BAC(+)-induced toxicity. In vitro toxic effects of antiglaucoma drugs could, in part, explain some ocular surface disorders in long-term treated patients.     

The phenol red thread first results for the assessment of the cut-off value in ocular sicca syndrome

PURPOSE: To determine the cut-off value of the phenol red-impregnated thread test (Zone-Quick((R)), Menicon trade mark ) for the diagnosis of ocular sicca syndrome using the ROC (receiver operating characteristic) procedure and to estimate the agreement with the Schirmer I test (without anesthetics). MATERIAL: and methods: Fifty-four consecutive patients (including 50 females) with dry eyes, presumably related to an immune disorder, were recruited on the basis of subjective ocular symptoms and medical history (sicca syndrome). Both the phenol red thread (PRT) test and the Schirmer I test (testing periods, 15s and 5min, respectively) were performed in both eyes in random order. Only the lowest result for each test was used in statistical analyses. The same procedure was applied to 29 normal volunteers (no subjective symptoms). The patient and the control groups were matched for age and gender (mean age, 58.1 and 59.6, respectively). RESULTS: The ROC procedure showed that a cut-off value of 12mm in the PRT test provided the best ratio between sensitivity and specificity (56% and 69%, respectively) for the detection of dry eyes. Using this threshold, the agreement with the Schirmer I test was highly significant (kappa test; P<10(-3)). However, discordant results were observed in 32% of subjects. CONCLUSION: Giving a cut-off value at 12mm, the sensitivity and specificity of the PRT are 56% and 69%, respectively. Even if the agreement with the Schirmer I test is highly significant, 32% of patients have discordant results. These two methods of functional assessment of tear secretion are therefore complementary and further studies remain necessary to better understand the place of both tests in clinical practice.     

Cornea in Marfan disease: Orbscan and in vivo confocal microscopy analysis

PURPOSE: To investigate corneal thickness, curvature, and morphology with the Orbscan Topography System I (Bausch & Lomb, Inc., Salt Lake City, UT) in patients with Marfan syndrome (MFS) and to study MFS with in vivo confocal microscopy. METHODS: This prospective, clinical, comparative case series included 60 eyes of 31 patients with MFS and 32 eyes of 17 control subjects. First, biomicroscopic examination was conducted to search for ectopia lentis. Then, mean keratometry and ocular refractive power were calculated by the autokeratorefractometer. In each group, the Orbscan System I mean (and mean simulated) keratometry and pachymetric measurements (at the central location and at eight midperipheral locations) were obtained and compared, and correlations were established. In vivo confocal microscopy was performed to evaluate tissue morphology and Z-scan analysis of 14 thin MFS corneas compared with 14 control corneas. RESULTS: A significant decrease (ANOVA, P < 0.0001) of mean simulated keratometry measurement appeared in the MFS group (sim K, 40.8 +/- 1.4 D) compared with the control group (42.9 +/- 1.1 D). Pachymetry in the MFS group was significantly decreased (P < 0.0001) compared with that in the control group, in the center (respectively, 502 +/- 41.9 microm and 552 +/- 23.6 microm) and the eight midperipheral locations. Ectopia lentis was highly linked with mean keratometry and pachymetry (P < 0.0001). Confocal microscopy performed on MFS-affected thin corneas confirmed the corneal thinning and showed an opaque stromal matrix, and Z-scan profiles were abnormal with increased stromal back scattering of light. CONCLUSIONS: MFS is known to be associated with a flattened cornea. This study demonstrated an association with corneal thinning and described confocal microscopy findings in this syndrome.     

Cytoprotective effects of hyaluronic acid and Carbomer 934P in ocular surface epithelial cells

PURPOSE: To investigate in vitro the cell toxicity and antioxidant effects of two major tear substitutes, hyaluronic acid and a widely used carbomer, with and without preservative. METHODS: Chang conjunctival cells were treated with different concentrations of unpreserved or preserved carbomer 934P (0.03% and 0.3%), unpreserved or preserved hyaluronic acid (0.018% and 0.18%), and benzalkonium chloride (BAC 0.0005% and 0.005%) for 15 minutes or for 15 minutes with 24 hours of cell recovery, according to previously validated methods. Microplate cold light cytofluorometry was performed to evaluate cell viability (neutral red test), chromatin condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests). Confocal microscopy was used to explore morphologic changes. RESULTS: No alterations were found with unpreserved and preserved hyaluronic acid at all concentrations and times tested. A decrease in cell viability with chromatin condensation appeared with 0.3% preserved carbomer 934P at the two times tested. This cytotoxicity, however, was significantly less than that observed with BAC alone, although the same concentrations of preservative were used. Unpreserved carbomer 934P induced no modification of cell viability after 15 minutes but a significant decrease in chromatin condensation, reversible after 24 hours of cell recovery, when a delayed decrease in cell viability was observed. Production of reactive oxygen species (ROS) decreased with the four formulations of tear substitutes tested at their usual concentrations, whereas a significant production of ROS occurred with BAC. CONCLUSIONS: These two ophthalmic hydrogels have no cytotoxicity but possess antioxidant properties and tend to reduce the toxic effects of preservatives. These results may allow use of hydrogels, not only in dry eye but also in ocular surface disorders involving oxidative stress and in ophthalmic drug therapy to improve ocular tolerance.