Paolo Fogagnolo

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.

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.

The Circadian Curve of Intraocular Pressure: Can We Estimate Its Characteristics during Office Hours?

PURPOSE To verify whether office-hour measurements in patients in different body positions can estimate the characteristics of 24-hour intraocular pressure (IOP). METHODS The 24-hour IOP curves of 29 healthy subjects (10 young adults, 19 elderly) and 30 patients with untreated glaucoma were analyzed. Measurements were taken at 9 AM; 12, 3, 6, and 9 PM; and 12, 3, and 6 AM, both in the supine and sitting (Goldmann tonometer) positions. Peak, mean, and fluctuation of 24-hour IOP curves were compared with office-hour measurements obtained in subjects in the sitting position alone and with combined pressures obtained in the sitting and supine positions (four measurements in each body position from 9 AM to 6 PM). The percentage of subjects with estimates of all IOP parameters within a cutoff of +/-1 (peak and mean) and +/-2 mm Hg (fluctuation) was calculated. RESULTS Office-hour sitting measurements correctly identified peak, mean, and IOP fluctuation in 10% of the young adults, 32% of the elderly control subjects, and 20% of the patients with glaucoma, whereas the combination of supine and sitting measurements correctly identified them in 30%, 85%, and 46% of cases, respectively. It is noteworthy that office-hour measurements did not characterize any 24-hour parameter in 20% of patients with glaucoma. CONCLUSIONS Compared with sitting measurements alone, the collection of supine and sitting office-hour measurements may enhance the correct identification of 24-hour IOP characteristics in both control subjects and untreated patients with glaucoma, thus reducing the need for obtaining 24-hour curves to a minority of patients.

Influence of Disc Size on Optic Nerve Head versus Retinal Nerve Fiber Layer Assessment for Diagnosing Glaucoma

PURPOSE To explore and compare the influence of optic disc size on the diagnostic accuracy of retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) quantitative assessment. DESIGN Observational, cross-sectional evaluation of diagnostic tests. PARTICIPANTS We included 120 eyes from 50 normal subjects and 70 glaucomatous patients classified by the presence of a repeatable visual field defect for the analysis. TESTING The RNFL thickness was measured by scanning laser polarimetry with variable corneal compensator (GDx-VCC, Carl-Zeiss Meditec, Dublin, CA) and spectral-domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec, Inc). We obtained ONH imaging by means of confocal scanning laser ophthalmoscopy (HRT3; Heidelberg Engineering, GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES Sensitivity and specificity for normative classifications, sensitivity at fixed specificity and area under the receiver operating characteristics curve (AUC) for continuous parameters. A logistic marginal regression model and coefficients of variation (CoV) have been used to test and quantify the influence of optic disc size on the diagnostic accuracy of the 3 technologies under investigation. RESULTS Among continuous parameters average RNFL thickness for Cirrus HD-OCT, nerve fiber indicator for GDx-VCC and cup shape measure for the HRT3 showed the best diagnostic accuracy with an AUC of 0.97, 0.94, and 0.94, respectively. Among normative classifications, the highest sensitivity and specificity were found for OCT average RNFL thickness (75.8% and 94.7%), for GDx superior thickness (77.1% and 97.5%), for HRT3 Moorfields regression analysis result (89.4% and 73.7%) and for HRT3 GPS global (92.3% and 76.5%). The diagnostic performance of HRT3 parameters seemed to be significantly influenced by optic disc size, although the same was not true for Cirrus HD-OCT and GDx VCC. The most steady performers for each imaging device across disc size groups were Cirrus HD-OCT average thickness (CoV, 1.6%), GDx-VCC inferior thickness (CoV, 2.5%), and HRT3 GPS temporal and nasal (CoV, 21.4%). CONCLUSIONS The diagnostic accuracy of quantitative RNFL assessment as performed by Cirrus HD-OCT and GDx-VCC is high and virtually unaffected or only minimally affected by the size of the optic disc and may provide more consistent diagnostic outcomes across small and large discs than ONH assessment as performed by HRT3.

Supraciliary shunt in refractory glaucoma

Aims This study aimed to evaluate the efficacy of Gold Micro Shunt (GMS) for suprachoroidal drainage in patients with refractory glaucoma. Methods This is a prospective uncontrolled case series study. Fifty-five eyes of 55 patients were included. Study eyes underwent GMS implantation in the supraciliary space. Follow-up visits were performed on day 1, week 1 and months 1, 3, 6, 12 and 24; patients underwent slit-lamp examination, Goldmann applanation tonometry, ultrasound biomicroscopy and gonioscopy. Results Before inclusion, the eyes underwent an average (±SD) of 1.9±0.7 (range 1–5) previous glaucoma surgery procedures. Forty eyes were pseudophakic, 12 were phakic and 3 were aphakic. The mean baseline intraocular pressure was 30.8±8.8 mm Hg (range 22–58 mm Hg) despite maximal medical treatment. After 2 years of follow-up, qualified success was achieved in 37 eyes (67.3%) and complete success was achieved in 3 eyes (5.5%). In success group patients, mean intraocular pressure decreased from 27.6±6.9 at baseline to 13.7±2.98 mm Hg after 2 years of follow-up; the mean (±SD) number of medications was 1.4±0.7 in the postoperative phase, compared with a value of 2.5±0.9 in the preoperative phase. Mild side effects occurred in 21 patients, with mild or moderate postoperative hyphema being the most frequent one. Development of a thin membrane, obstructing the anterior holes, was the most important factor affecting the efficacy of this device; it was found to be present in 12 patients from the failure group (66.7% of failures). Conclusion GMS achieved qualified success in about 67.3% of eyes with uncontrolled refractory glaucoma with a low rate of complications.

A review of the use of latanoprost for glaucoma since its launch.

Introduction: Prostaglandins are increasingly used as first choice treatment for glaucoma because they are highly effective, lack relevant systemic side effects and require just once-daily administration. Latanoprost is an ester prodrug analog of prostaglandin F2α, which reduces intraocular pressure (IOP) by increasing uveoscleral outflow. Latanoprost 0.005% has received European and US approval as the first-line drug for reducing IOP in patients with open-angle glaucoma or ocular hypertension. Following the recent patent expiry for Xalatan®, a number of latanoprost generics have entered the glaucoma market. Areas covered: This review, achieved through PubMed and Medline research methods, describes the composition, pharmacokinetics, mode of action, efficacy, side effects and safety profile of latanoprost. Expert opinion: Latanoprost was the first prostaglandin analog introduced in glaucoma management and it dramatically changed the market of the disease thanks to its efficacy and safety. Conjunctival hyperemia, which is commonly found after latanoprost use, is associated with a minor efficacy and duration of trabeculectomy; yet, from the ophthalmologists perspective, this side effect seems largely counterbalanced by the high efficacy and safety of this compound. It is always advisable to consider the pro-inflammatory mode of action of latanoprost because this may have negative effects in particular patients (i.e., those with uveitis and cystoid macular edema) for whom caution and close follow-up is necessary.

Efficacy of the fixed combinations of bimatoprost or latanoprost plus timolol in patients uncontrolled with prostaglandin monotherapy: A multicenter, randomized, investigator-masked, clinical study

Purpose To compare the efficacy and tolerability of a once-daily evening dose of bimatoprost/timolol fixed combination (BTFC) with that of a once-daily evening dose of latanoprost/timolol fixed combination (LTFC) in patients not controlled with prostaglandins analogues monotherapy. Methods A total of 82 patients on prostaglandin analogues monotherapy were enrolled in this prospective, multicenter, investigator masked, clinical study and were randomized to either BTFC (n=47) or LTFC (n=35) topical therapy once at night for 12 weeks. The primary endpoint of the study was to compare the mean daily intraocular pressure (IOP) reduction from baseline between the two treatment arms. Secondary endpoints included the mean daily IOP at 1 and 3 months compared to baseline and the percentage of patients showing a mean IOP reduction from baseline greater than or equal to 15% or 20%. Results Mean IOP at baseline was 22.7±2.0 and 22.1±2.6 mmHg in the BTFC and LTFC groups, respectively (p=0.23). Both treatments were effective in reducing the IOP from baseline. The mean IOP reduction was significantly greater in the BTFC group than in the LTFC group (–21.4% vs −13.7%, p<0.001). A higher percentage of patients in the BTFC group showed a mean IOP reduction from baseline ≥ 15% (72.3% vs 40.0%) and ≥ 20% (61.7% vs 17.1%) compared to patients in the LTFC group. Conclusions Both BTFC and LTFC were more effective versus the monotherapy with prostaglandin analogues. BTFC demonstrated higher performance than LTFC in terms of relative IOP reduction.

Sector-Based Analysis with the Heidelberg Retinal Tomograph 3 Across Disc Sizes and Glaucoma Stages: A Multicenter Study

PURPOSE To investigate the ability of sectorial analysis using the Heidelberg Retinal Tomograph 3 (HRT3) to discriminate between healthy and glaucomatous eyes and to determine whether this is affected by disc size and glaucoma severity. DESIGN Multicenter, cross-sectional evaluation of diagnostic tests. PARTICIPANTS Two hundred thirty-three eyes from 137 normal subjects and 96 glaucoma patients classified by the presence of a repeatable visual field defect. TESTING Participants underwent imaging with the HRT3, and the diagnostic accuracy of stereometric parameters, Moorfields regression analysis (MRA), and glaucoma probability score (GPS) were analyzed sectorially by glaucoma stage and optic disc size. MAIN OUTCOME MEASURES Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristics curve (AUC). RESULTS Of stereometric parameters, the cup-to-disc area ratio of the inferotemporal sector had the largest AUC (AUC, 0.74). Both MRA and GPS algorithms showed the best diagnostic accuracy in the inferotemporal sector, with a sensitivity and specificity of 63% and 88% for MRA and 80% and 62% for GPS, respectively. In small discs, sectorial MRA analysis had higher diagnostic accuracy than the global optic nerve head (ONH) analysis (sensitivity of 70% and specificity of 82% in the inferonasal sector), and these findings were confirmed in very large discs (sensitivity of 74% and specificity of 85% in the inferotemporal sector). Similarly, stereometric parameters discriminated better sectorially rather than globally, with different parameters giving the best results in different optic disc size subgroups. MRA sensitivity was weak in the early-glaucoma stage, with slightly higher figures if considered sectorially rather than globally. GPS diagnostic accuracy was very consistent across ONH sectors in each disc size and glaucoma stage subgroup, with no single sector demonstrating better diagnostic accuracy than the global analysis. CONCLUSIONS Heidelberg Retinal Tomograph 3 sectorial analysis showed moderate diagnostic performance and may offer potential advantages over global analysis in the clinical diagnostic process. Small discs are classified more accurately by examining the inferonasal sector, whereas larger discs are classified more accurately by examining the inferotemporal sector. Neither HRT parameters nor classification algorithms seem to be good at the earlier stage of the disease. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Long-term perimetric fluctuation in patients with different stages of glaucoma

Aim To evaluate the long-term perimetric fluctuation (LF) in patients with different stages of glaucoma according to the Glaucoma Staging System 2 (GSS2). Methods This multicentre retrospective study included 161 eyes of 161 stable glaucoma patients undergoing four visual-field tests (Humphrey SITA-Standard program over the central 24° or 30°) over a 2-year period. For each patient, the stage of the disease was classified according to GSS2. LF was then calculated as the mean of the standard deviations of point-to-point threshold sensitivities in the four repetitions. LF in GSS2 stages was compared using the t test. Results LF progressively increased from stage 0 to stage 4, and then decreased at stage 5. Stage 4 had a peak of 3.19±0.94 dB, with statistically significant differences compared with all the other stages. The lowest LF (1.65±0.60 dB) was found for normal subjects, whereas similar data were found for borderline patients and those at stages 1 and 5 (2.09±0.58, 2.13±0.57 and 2.22±0.89 dB, respectively; p>0.13). Visual fields with generalised defects had a lower LF (1.90±0.81) than those with mixed (2.84±0.87, p=0.0003) and localised (2.63±0.72, p=0.004) defects. Conclusions In this study, the authors showed that the lower the visual-field defect, the lower was LF, except at stage 5 of GSS2. As test–retest changes exceeding LF could represent a sign of progression, the authors suggest that clinicians using this classification system calculate LF, in order to better differentiate true progression from variability.

Learning effect of short-wavelength automated perimetry in patients with ocular hypertension.

AimTo evaluate the learning effect of short-wavelength automated perimetry (SWAP) on a group of patients with ocular hypertension experienced with standard automated perimetry (SAP). MethodsThirty patients with ocular hypertension underwent 5 full-threshold SWAP tests at intervals of 7±2 days. The parameters investigated to detect a learning effect were duration, the perimetric indices, and the number of points with a P of <5% and 1% in the total and pattern deviation maps. Differences in learning effect were also evaluated by comparing the sensitivities of central, paracentral, and peripheral areas, hemifields and quadrants. ResultsLearning effects were demonstrated for mean defect (P<0.0001, analysis of variance), duration (P=0.0001), the number of points with P<5% in the pattern deviation map (P=0.003), and short fluctuations (P=0.03). The effect was greater in the peripheral than in central areas (P=0.04). Mean defect was the most sensitive parameter, for which the learning effect was statistically significant between the first and the fifth test. ConclusionsThe results of this study demonstrate a significant learning effect at full-threshold SWAP. This may limit the efficacy of this kind of perimetry in detecting early glaucoma, and should therefore be carefully considered when creating normative databases for new SWAP strategies.