Luca Rossetti

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

Medical prophylaxis and treatment of cystoid macular edema after cataract surgery. The results of a meta-analysis.

OBJECTIVE The study aimed to determine the effectiveness of prophylactic medical intervention in reducing the incidence of cystoid macular edema (CME) and the effectiveness of medical treatment for chronic CME after cataract surgery. DESIGN The study design was a systematic review and meta-analysis of published reports of randomized clinical trials (RCTs). PARTICIPANTS Sixteen RCTs involving 2898 eyes examining the effectiveness of medical prophylaxis of CME and 4 RCTs involving 187 eyes testing the effectiveness of medical treatment of chronic CME were used in the study. INTERVENTIONS Medical prophylaxis of treatment (cyclo-oxygenase inhibitors or corticosteroids) versus control (placebo or active treatment) was performed. MAIN OUTCOME MEASURES Incidence of angiographically diagnosed CME, incidence of clinically significant CME, and vision were measured. RESULTS Thirty-six articles reported testing a prophylactic medical intervention for CME after cataract surgery. The incidence of CME varied extensively across studies and was related to the study design used. Summary odds ratios (OR) indicated that prophylactic intervention was effective in reducing the incidence of both angiographic CME (OR = 0.36; 95% confidence interval [CI] = 0.28-0.45) and clinically relevant CME (OR = 0.49; 95% CI = 0.33-0.73). There also was a statistically significant positive effect on improving vision (OR = 1.97; 95% CI = 1.14-3.41). A combination of the results of the four RCTs testing medical therapy for chronic CME indicated a treatment benefit in terms of improving final visual acuity by two or more Snellen lines (OR = 2.67; 95% CI = 1.35-5.30). Assessment of the quality of the 20 RCTs included in the meta-analyses indicated problems in the design, execution, and reporting of a number of trials. CONCLUSION A combination of the results from RCTs indicates that medical prophylaxis for aphakic and pseudophakic CME and medical treatment for chronic CME are beneficial. Because most of the RCTs performed to date have problems related to quality, a well-designed RCT is needed to confirm this result, using clinical CME and vision as outcomes.

Intraobserver and interobserver reproducibility in the evaluation of optic disc stereometric parameters by Heidelberg Retina Tomograph

PURPOSE To assess intraobserver and interobserver reproducibility of the measurement of stereometric parameters of the optic disc by means of the Heidelberg Retina Tomograph I (HRT). STUDY DESIGN Observational study, with interobserver variability. PARTICIPANTS Fifty-five volunteers (healthy subjects and patients with glaucoma). METHODS HRT examination of the optic disc was repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each session, five single images were randomly acquired by two independent observers. One mean topography image (MTI), based on three single images, was then built at each session. For the intraobserver intraimage evaluation, the two observers traced their own contour line on one randomly chosen MTI. This procedure was repeated three times. For the intraobserver interimage and interobserver intra/interimage evaluations, the two observers traced their own contour line on the MTI of the first session, which was then automatically superimposed on the MTIs of the other two sessions. MAIN OUTCOME MEASURES Reproducibility of the 12 stereometric parameters was calculated for each observer by means of the intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated by the scatter-plots of each test-retest difference versus their mean. The standard deviation of the mean test-retest score differences was used to describe the spread of score differences. RESULTS The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for the interobserver interimage evaluation. ICC was almost perfect to perfect for planimetric measures (0.81 < ICC < or = 1), substantial to almost perfect for volumetric and cup measures (0.61 < ICC < or = 0.99), and moderate to almost perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The expected variability was low (95% confidence interval, < +/-9%). Interimage evaluation showed a higher variability than intraimage evaluation in both of interobserver (P = 0.012) and intraobserver evaluation (P = 0.028 and P = 0.031 for the two observers). CONCLUSIONS Measurement of optic disc stereometric parameters by HRT is highly reproducible. However, the use of retinal nerve fiber layer-related parameters should be taken cautiously. The image acquisition-induced variability seems larger than the operator-induced variability.

Cystoid macular edema following cataract surgery.

Cystoid macular edema (CME) remains a troublesome problem after cataract surgery and other types of ocular surgical procedures. It is recognized as the most frequent cause of decreased vision in patients following cataract surgery. Although the disease was first described more than 40 years ago, its cause is unclear, and all available therapeutic interventions, mainly based on theories regarding the pathogenesis of the condition, are of doubtful effectiveness and are still far from being satisfactory. Most published literature on the incidence and treatment of CME consists of small, retrospective case series and cannot provide reliable answers as to whether a given factor or intervention is associated with the occurrence or outcome of the disease.

Beware of Surrogate Outcome Measures

Surrogate outcome measures may speed up clinical research if they can be measured earlier in a study than the primary outcome of interest. We review the justification for their use and conclude that reliance on them may be harmful. Results obtained with surrogates should therefore be regarded as preliminary. Large, definitive trials with clinically relevant outcomes should always be performed before new interventions are accepted.

Randomized clinical trials on medical treatment of glaucoma: Are they appropriate to guide clinical practice?

A systematic quantitative and qualitative overview of published randomized clinical trials was undertaken to assess the yield of medical treatment on the outcome of patients with primary open angle glaucoma. Reports of 102 randomized clinical trials were published between 1975 and 1991, totalling about 5000 patients. Only 16% (16/102) of the trials were, however, properly designed (ie, comparing an active treatment with a placebo-treated or untreated control group) to answer the question of whether any medical treatment can effectively cure patients with primary open angle glaucoma. Pooled analysis showed a moderate yet statistically significant reduction in mean intraocular pressure (-4.9 mm Hg; 95% confidence interval [CI], -7.3 to -2.5 mm Hg); however, data on long-term visual field changes were available in only three randomized clinical trials, and their statistical combination failed to show a significant protective effect of active treatment (odds ratio, 0.75; 95% CI, 0.42 to 1.35). All of the remaining 86 randomized clinical trials looked at the effectiveness of one drug vs another in lowering intraocular pressure and were thus of no use in the overview. Practicing ophthalmologists should be aware that the effectiveness of pressure-lowering agents in the treatment of primary open angle glaucoma is still to be determined and that the vast majority of published trials are not appropriate to guide clinical practice. It is urgent to plan trials with end-point and follow-up duration that is fully relevant for the health of patients.

Corneal Subbasal Nerves Changes in Patients with Diabetic Retinopathy: An In Vivo Confocal Study

PURPOSE To study the subbasal corneal plexus (SCP) in patients with diabetic retinopathy (DR) treated or nontreated with panretinal Argon laser photocoagulation (ALP). METHOD Fifty consecutive patients with DR and 50 age- and sex-matched normal control subjects were examined with retinal tomography by a masked evaluator. The following subbasal plexus nerves parameters were considered: number per frame, tortuosity, and reflectivity. Diabetic patients were divided into two groups, according to the presence of proliferative versus nonproliferative retinopathy, according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification. RESULTS The number of fibers per frame and reflectivity were significantly lower in diabetic patients compared with control subjects (2.4 +/- 1 vs. 2.9 +/- 0.8, P = 0.01 and 2.3 +/- 0.9 vs. 2.6 +/- 0.9, P = 0.04, respectively). Tortuosity was significantly higher in diabetic patients (2.5 +/- 0.9 vs. 2.0 +/- 0.8, P = 0.002). Number per frame and reflectivity were significantly lower in diabetic patients with proliferative diabetic retinopathy (PDR; respectively, 2.0 +/- 0.9 vs. 2.9 +/- 0.9, P = 0.001, and 2.0 +/- 0.8 vs. 2.6 +/- 0.7, P = 0.003). Tortuosity was significantly higher in the PDR group (2.2 +/- 0.8 vs. 2.8 +/- 0.9, P = 0.008). The PDR group treated with ALP had significantly lower subbasal nerves number compared with the nontreated group (P = 0.01). CONCLUSIONS DR may induce substantial changes in the SCP. There is a difference between proliferative and nonproliferative retinopathy and in the former group between ALP treated and nontreated patients.

Performance of diffractive multifocal intraocular lenses in extracapsular cataract surgery

Abstract In a prospective, randomized clinical trial, 42 patients received a monofocal intraocular lens and 38 a multifocal lens after extracapsular cataract extraction. Patients were examined three, six, and 12 months after surgery. Uncorrected visual acuity was 20/40 or better in 57% of monofocal and 58% of multifocal patients; 12% and 52% had near uncorrected visual acuity of J1 to J2, respectively. Best corrected visual acuities were not significantly different. Forty‐eight percent of the multifocal and 8% of the monofocal group did not require spectacle correction. On a patient satisfaction questionnaire, 60% of all patients reported discomfort when using spectacles for near vision. Patients in the multifocal group were more satisfied with their near vision than those in the monofocal group. The difference in satisfaction was not significantly different although more multifocal patients reported visual phenomena (e.g., glare, halos). Mean contrast sensitivity for the monofocal group and the multifocal group was 1.73 and 1.70, respectively. At low contrast sensitivities, the difference was not significant although the monofocal patients scored better.

Prevalence of retinopathy in patients with anemia or thrombocytopenia.

Abstract: Background and objectives: Fundus lesions can be the accompanying symptom in many hematological diseases. In cases of anemia or thrombocytopenia, the exact mechanism leading to fundus abnormalities is not completely understood. The aim of this study was to calculate the prevalence of fundus lesions in anemic and thrombocytopenic patients, and define the risk factors for retinopathy. Design and methods: This cross‐sectional study involved 226 patients with anemia and/or thrombocytopenia and a control group of 47 age‐matched subjects. The studied variables were age, gender, hemoglobin levels, mean cell volume (MCV), red cell distribution width coefficient variation (RDW‐CV), the type of onset of anemia, platelet counts, mean platelet volume (MPV), platelet distribution width (PDW), the platelet–large‐cell ratio (P‐LCR), prothrombin time (PT) and partial thromboplastin time (PTT). Results: Retinopathy was observed in 28.3% of the patients as a whole, the presence of fundus lesions being closely associated with severe anemia (Hb < 8 g/dL) and severe thrombocytopenia (PLT < 50 × 109/L). Among the patients with concomitant anemia and thrombocytopenia, the incidence of retinopathy was 38%. Age, low hemoglobin levels, platelet counts, RDW‐CV, and increased MCV, MPV and P‐LCR were all significantly associated with the presence of fundus lesions at univariate analysis. Interpretation and conclusions: Retinopathy is a frequent finding in anemic and thrombocytopenic patients, although it is often not significant clinically. As retinal hemorrhages were found in all of the patients with concomitant severe anemia and thrombocytopenia, it is recommended that all such patients undergo routine fundus examinations.

Circadian variations in central corneal thickness and intraocular pressure in patients with glaucoma.

Aim: To analyse 24 hour variations in intraocular pressure (IOP) and central corneal thickness (CCT) in a group of glaucomatous patients. Methods: 30 patients with primary open angle glaucoma were hospitalised and underwent circadian evaluations (at 8 pm, midnight, 4 am, 8 am, noon, and 4 pm) of supine and sitting IOP, respectively, measured using a Perkins and a Goldmann tonometer, and CCT measured using an ultrasonic pachymeter (the mean value of three measurements within 5 μm). All patients were treated with timolol 0.5% twice daily and latanoprost 0.005% once daily. Results: Mean supine IOP was 15.3 (SD 3.7) mm Hg (range 10–25), with circadian fluctuations of 7.3 (3.3) mm Hg. Mean sitting IOP was 15.1 (3.9) mm Hg (range 8–26), with circadian fluctuations of 5.4 (3.1) mm Hg. Mean CCT was 534 (39) μm (range 443–637 μm) with circadian fluctuations of 16.5 (6.2) μm (range 6–31 μm). Both the within patient and within time point fluctuations in CCT were statistically significant (p<0.0001, ANOVA). Conclusions: The authors found considerable fluctuations in 24 hour IOP. The circadian fluctuations in CCT were small and, although statistically significant, did not seem to interfere with the circadian IOP assessment.