Nicola Orzalesi

Intraobserver and interobserver reproducibility in the evaluation of ultrasonic pachymetry measurements of central corneal thickness

Purpose: To assess reproducibility of central corneal thickness (CCT) measurement by means of ultrasonic pachymetry. Methods: Fifty one volunteers underwent three sessions of CCT measurements, each consisting of three CCT measurements, performed by each of three different observers. Intra- and interobserver reproducibility was calculated by means of intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated using scatter plots of each test-retest difference against their mean. The standard deviation of the mean differences in the test-retest scores was used to describe the differences in the score spread. Results: The ICC ranges of the intra- and interobserver evaluations were 0.95–0.97 and 0.89–0.95 respectively; the expected variability was ⩽±1% and ⩽± 2% respectively (95% confidence interval). Conclusions: The measurement of CCT by means of ultrasonic pachymetry is highly reproducible.

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.

Studies on the fine structure and the rhodopsin cycle of the rabbit retina in experimental degeneration induced by sodium iodate

The authors investigated the ultrastructure and the rhodopsin cycle of the rabbit retina by experimental degeneration with sodium iodate. The first ultrastructural changes were observed in the pigment opithelium, whose cells showed early and severe involvement ending in complete destruction within a few days. A swelling of the outer side of the Muller cells and the degeneration of the outer segments of the visual cells followed the damage to the pigment opithelium. In the advanced stages of the treatment, the degenerated cells of the pigment epithelium were replaced by modified pigment cells. These new cells had peculiar cytological features and marked phagocytic activity toward fragments of the outer segments of the photoreceptors and of the disrupted pigmented cells. Similar degenerative changes developed in the animals treated under conditions of light and dark adaptation. In the light-adapted rabbits, however, the rhodopsin measurements revealed an early decrease of the rhodopsin concentration in the retinas treated with sodium iodate, whereas in the dark-adapted rabbits, normal levels of the photopigment were recorded. It is suggested, therefore, that the degeneration of the retinal pigment epithelium could block the process of resynthesis of the rhodopsin under light-adaptation conditions. This suggestion supports the hypothesis that important processes of the rhodopsin cycle, specially the isomerization of vitamin A and of retinene, can be performed only in this retinal layer. Moreover, the fact that the degeneration of the outer segments of photo-receptors always followed severe damage to the pigment epithelium may indicate the existence of some nutritional dependence of the visual cells on the pigmented ones. The experimental degeneration of the retina as a new tool for studying the retinal function is of great importance. In fact, the selective manner in which metabolic poisons affect the different retinal layers allows one to evaluate the morphological and functional effects caused by the blocking activity in these layers.

Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography.

OBJECTIVE This study aimed to determine whether the indocyanine green angiography (ICGA)-guided laser treatment of feeder vessels (FVs) may be useful in the management of the subfoveal choroidal neovascular membranes (CNVM) in patients with age-related macular degeneration (ARMD). DESIGN Noncomparative case series. PARTICIPANTS The authors considered a series of 15 patients with subfoveal CNVM in whom feeder vessels could be clearly detected by means of dynamic ICGA but not necessarily with fluorescein angiography (FA). On the basis of the indications of the pilot study, the authors also studied a second series of 16 patients with FVs smaller than 85 microm. INTERVENTION Treatment of FV using argon green laser was performed. The ICGA was performed immediately after treatment, after 2, 7, 30 days, and then every 3 months, to assess FV closure. If an FV appeared to be still patent, it was immediately retreated and the follow-up was started again. The follow-up time ranged from 23 to 34 months for the pilot study and from 4 to 12 months for the second series. MAIN OUTCOME MEASURES The obliteration of the membrane and change in visual acuity from baseline were measured. The effect on the treatment of the number and width of the FVs, and the size and location of the membrane, also was evaluated. RESULTS In the pilot study, the CNVM was obliterated after the first treatment in only one patient, five patients needed more than one treatment, and obliteration failed in nine patients (40% success rate). The rate of success was affected by the width and number of the FVs. The success rate in the second series of 16 patients was higher (75%). CONCLUSIONS The success of the laser treatment of FVs depends on their width, length, and number. Dynamic ICGA, which detects smaller FVs and makes it possible to control the laser effect and initiate immediate retreatment in the case of incomplete FV closure, should be considered mandatory for this type of treatment; a comparable success rate would have been unlikely using the other currently available methods of treating subfoveal CNVMs.

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.

Retinal angiomatous proliferation: natural history and progression of visual loss.

Purpose: To investigate the natural history and visual outcome in eyes with untreated retinal angiomatous proliferation, a neovascular form of age-related macular degeneration. Methods: Fourteen consecutive white patients (11 women, 78%; mean age, 74 years) with 16 eyes affected by retinal angiomatous proliferation were prospectively followed-up without treatment by means of complete ophthalmologic examinations at regular intervals, including best-corrected visual acuity and dynamic fluorescein and indocyanine green angiography using a scanning laser ophthalmoscope. Results: The patients were observed for a mean of 20 months (range, 6–44 months). Mean visual acuity in the eyes with retinal angiomatous proliferation was 0.48 at the initial examination, decreased to 0.23 after 6 months, and was 0.19 at the final examination, with a mean decrease of 6 lines from baseline. In 13 eyes (81%), visual acuity deteriorated by 2 Early Treatment Diabetic Retinopathy Study lines or worse by the time of the 6-month examination, and 31% of the patients had experienced severe loss of vision; the remaining 3 eyes (19%) showed a relatively stable clinical course and visual acuity. By the time of the final examination, visual acuity had decreased to 0.1 or worse in 11 eyes (69%), and 5 of the 14 patients (36%) were legally blind. At the final examination, 10 eyes (62%) showed a subretinal fibrosis and 9 (56%) showed a retinal choroidal anastomosis. Conclusion: Retinal angiomatous proliferation is a distinct form of neovascular age-related macular degeneration with high vasogenic potential, having its own clinical course and visual prognosis. The poor visual outcome is because of the exudative nature of the retinal angiomatous proliferation, and progression to poor vision is common and rapid (within 3 months in faster cases, and within 1 year in slower cases). The treatment options for this type of neovascular lesion should be planned bearing in mind its unfavorable natural history.

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.

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.

Microperimetry of localized retinal nerve fiber layer defects

The aim of this study was to determine the sensitivity of retinal areas involved in a localized retinal nerve fiber layer (RNFL) defect and to assess correlations between microperimetry and the standard full threshold central 30 deg visual field test. Twenty-five patients with focal RNFL defects, evaluated by means of Argon-blue scanning laser ophthalmoscopy (SLO), underwent an automated 30 deg central visual field examination and a microperimetry with SLO. Microperimetry was performed according to standard procedures (infrared laser for fundus imaging; HeNe laser for 10 candles/m2 background illumination, fixation aid and generation of stimuli; manual fundus tracking). The size of stimuli was Goldmann III with 0.1 sec duration. In eyes with focal RNFL defects a deep microperimetric scotoma of at least 5 dB was found in 12 cases and a mild scotoma (1-4 dB) in 13 cases. These scotomas were mainly located throughout the whole defect or grouped in the temporal or nasal sides of the defect and were characterized by sharp and well-defined borders. With automated perimetry, a scotoma, defined by a single point depression of at least 10 dB or a depression of at least 5 dB in two or more contiguous points corresponding to the RNFL, defect, was found in only 14 out of 25 eyes with microperimetric defect. Focal RNFL defects correspond to localized areas of depressed retinal sensitivity as evaluated by microperimetry. The close correspondence between structural and microperimetric findings suggests that, in hypertensive eyes also, localized RNFL defects correspond to visual dysfunction possibly associated with substantial atrophy of ganglion cells.