G. Corallo

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.

Agreement to detect glaucomatous visual field progression by using three different methods: a multicentre study.

Aim To examine the level of agreement among nine clinicians in assessing progressive deterioration in visual field (VF) overview using three different methods of analysis. Methods Each visual field was assessed by Humphrey Field Analyzer (HFA), program 24-2 SITA Standard. Nine expert clinicians assessed the progression status of each series by using HFA ‘overview printouts’ (HFA OP), the Guided Progression Analysis (GPA) and the Guided Progression Analysis (GPA2). VF series were presented in random order, but each patients VF remained in chronological order within a given field series. Each clinician adopted his personal methods based on his knowledge to evaluate VF progression. The level of agreement between the clinicians was evaluated by using weighted κ statistics. Results A total of 303 tests, comprising 38 visual field series of 7.9±3.4 tests (mean±SD), were assessed by the nine glaucoma specialists. When the intra-observer agreement was evaluated between HFA OP and GPA, the mean κ statistic was 0.58±0.13, between HFA OP and GPA2, κ was 0.55±0.06 and between GPA and GPA2 it was 0.56±0.17. When the inter-observer agreement was analysed κ statistic was 0.65 for HFA OP, 0.54 for GPA and 0.70 for GPA2. Conclusions Using any procedure for evaluating the progression of a series of VF, agreement between expert clinicians is moderate. Clinicians had higher agreement when GPA2 was used, followed by HFA OP and GPA printouts, but these differences were not significant.

A comparative study of computerised visual field testing and optic disc morphometric parameters in the follow-up of primary open angle glaucoma

Purpose To evaluate the correlation between computerised visual field testing and optic disc morphometric parameters (rim area, rim/ disc area ratio, cup/disc area ratio and optic disc surface smoothness (ODSS)) in the follow-up of a group of patients affected by primary open angle glaucoma (POAG).Methods Reliable automated perimetry (Humphrey 640 VFA, central 30-2 threshold program) was performed at T0 (the enrolment time), T1 (after 6 ± 1 months;range 5-7 months), T2 (12 ± 1 months), T3 (18 ± 1 months), and T4 (the end of the follow-up period: 24 ± 2 months) in one eye randomly chosen from each of 30 POAG patients. Computerised optic disc analysis (IMAGEnet X Rev-3-51b, Topcon Europe, The Netherlands) was performed at T0 and T4. To evaluate the correlation between morphometric parameters and computerised visual field testing, the stability or worsening of visual field test was evaluated by means of ‘Mean Deviation linear regression analysis’ (STATPAC 2 software); that of morphometric parameters was studied using their coefficients of variation. A rank of ′0′ was assigned to stability and a rank of ″1″ to worsening. The Spearman rank correlation coefficient was used to evaluate statistically the correlations between visual field analysis and morphometric parameters. Furthermore kappa statistic was used to evaluate the agreement of morphometric parameter changes with visual field progression analysis.Results According to the MD slope regression analysis, in 18 patients the visual fields were stable while in 12 they were worsening during the follow-up period. In 86.65% of patients (n = 26) the morphometric parameter ODSS and visual field analysis were concordant (p <0.0001). In 80% of patients (n = 24) the cup/ disc area ratio and visual field analysis were concordant (p < 0.001). The other morphometric parameters (rim area, rim/disc area ratio) were less correlated with visual field analysis than ODSS (p < 0.05). The agreement of visual field analysis with all the morphometric parameters was good (kappa = 0.690, 95% confidence interval (CI) of kappa = 0.589-0.790). The agreement of visual field analysis with ODSS and cup/disc area (kappa = 0.688;95% CI = 0.511-0.864) was better than the agreement of visual field analysis with rim area and rim/disc area ratio (kappa = 0.438;95% CI = 0.260-0.655).Conclusion Analysis of the progression of visual field damage and optic nerve head morphometric parameters should both be taken into account in glaucoma follow-up. Among the morphometric parameters evaluated by means of Topcon IMAGEnet, ODSS and (to a lesser extent) the cup/disc ratio should have the greatest weight.

Agreement in detecting glaucomatous visual field progression by using guided progression analysis ?and Humphrey overview printout.

Purpose To examine the level of agreement among 3 clinicians in assessing glaucoma visual field progression by using 2 different methods. Methods Each visual field was assessed by Humphrey Field Analyzer (HFA), program SITA standard 30–2 or 24–2. In each printout the first 3 fields were excluded to minimize learning effect: the fourth and fifth full-threshold or SITA Standard examinations were used as baseline. Three clinicians assessed the progression status of each series using both HFA overview printouts and the guided progression analysis (GPA). The level of agreement among the clinicians was evaluated using a weighted kappa statistic (κ). Results A total of 510 tests, comprising 83 eyes with an average of 6.1 tests each, was assessed by the 3 specialists. The mean follow-up time was 5.8±1.75 years (mean ± standard deviation). When the intraobserver intermethod agreement was evaluated, κ ranged from 0.5 to 0.7. When the interobserver agreement was analyzed, if HFA overview printouts were used, κ ranged from 0.4 to 0.7. But when GPA was used, κ ranged from 0.2 to 0.6. The level of agreement on progression status between the clinicians was always higher when they used HFA overview printouts (median κ = 0.54) than when they used GPA (median κ=0.37). Conclusions Agreement among expert clinicians about visual field progression status was moderate when GPA printouts were used. Clinicians’ agreement about patients’ visual field progression status was better when HFA overview printouts were used than with GPA printouts.

Rarebit perimetry and frequency doubling technology in patients with ocular hypertension

Purpose To test the capability of rarebit perimetry (RP), a recent non-conventional perimetric technique, in detecting early functional damage in subjects with ocular hypertension (OHT) and to compare RP findings with those obtained by frequency-doubling technology (FDT) perimetry. Methods Thirty patients with OHT were matched with 30 healthy subjects. All were tested with RP and FDT. Frequency-doubling technology mean deviation (MD) and pattern standard deviation (PSD), as well as RP mean hit rate (MHR), of the two groups were analyzed. The agreement between the two techniques was tested by Kappa analysis. Results In the OHT group the mean (SD) FDT MD was 0.5 (2.1), the mean (SD) FDT PSD was 4.2 (1.6), and the mean (SD) RP MHR was 81.4 (6.7). In the control group, corresponding values were mean (SD) FDT MD 1.1 (1.4), mean (SD) FDT PSD 3.0 (0.3), mean (SD) RP MHR 96.2 (2.0). The differences between the two groups were not significant for the studied indexes. Eleven (36.6%) out of the 30 OHT eyes had abnormal RP results; 12 (40.0%) eyes had abnormal FDT results. Five (16.6%) eyes had abnormal RP and FDT findings. Only 1 eye (3.3%) in the control group had abnormal RP results and 3 eyes (10.0%) had abnormal FDT results. RP and FDT showed a moderate agreement (Kappa = 0.43; 95% CI: 0.42 to 0.51). Conclusions RP and FDT showed VF defects not shown in standard automated perimetry in the OHT group. This may be indicative of an increased risk in developing glaucoma, even if a gold standard for detecting subtle defects is not currently available. RP has the additional advantage of not requiring any expensive device to be used. The poor agreement between these techniques in identifying eyes with early damage warrants further investigations. Large longitudinal studies are needed before defining the role of RP in early glaucoma diagnosis.

Learning effect in perimetry: the role of chromatic discrimination.

p a J t t f by our image analysis algorithm, and therefore the statistical comparison of the results is valid. These results cannot be compared to the database of the Spectralis instrument, since a different algorithm was used for generating the data. A review of literature clearly documents differences in thickness measurements between different instruments, stemming from the depth location of the chorioretinal interface. For these reasons, in fact, comarison of our measurements to the instrument database as uggested would be flawed. It was also astutely pointed out that central subfield nalysis would be useful and clinically meaningful. More xtensive work on this topic exploring focal retinal thining in ETDRS-like macular subfields or more temporal atershed region by SD-OCT, with frequency of focal etinal thinning stratified by stage of retinopathy as well as ickle cell genotype, is currently in submission.

Static Automated Perimetry in the Follow-Up of Lens Opacities

Modern perspectives of cataract medical therapy have induced researchers to study objective methods for the evaluation of lens transparency. Visual acuity determination, slit-lamp examination, photographic and densitometric methods have poor reliability. In this study computerized static perimetry was tested and our strategy was based on two automatic perimeters: Peritest (Rodenstock) and Perikon (Optikon). Peritest was very useful in the static analysis of cataract-induced threshold changes in the central visual field. Static meridional perimetry by Perikon was utilized to study peripheral threshold changes. This method, tested in 50 patients (25 under therapy with anti-cataract drugs) appeared to be reliable, rapid, easily standardized and well-accepted by patients.