Antonio Ferreras

Can frequency-doubling technology and short-wavelength automated perimetries detect visual field defects before standard automated perimetry in patients with preperimetric glaucoma?

PurposeTo assess the ability of frequency-doubling technology (FDT) perimetry and short-wavelength automated perimetry (SWAP) to detect glaucomatous damage in preperimetric glaucoma subjects. ParticipantsTwo hundred seventy-eight eyes of 278 subjects categorized as normal eyes [n=98; intraocular pressure <20 mm Hg, normal optic disc appearance, and standard automated perimetry (SAP)]; preperimetric glaucoma eyes (n=109; normal SAP and retinal nerve fiber layer defects or localized optic disc notching and thinning); and glaucoma patients (n=71; intraocular pressure >21 mm Hg, optic disc compatible with glaucoma, and abnormal SAP). MethodsThe preperimetric glaucoma group underwent at least 2 reliable full-threshold 24-2 Humphrey SAPs, full-threshold C-20 FDT, full-threshold 24-2 SWAP, optic disc topography using the Heidelberg Retina Tomograph II, laser polarimetry using the GDx VCC, and Optical Coherence Tomography (Zeiss Stratus OCT 3000). Receiver operating characteristic curves were plotted for the main Heidelberg Retina Tomograph, Optical Coherence Tomography, and GDx VCC parameters for the normal and glaucoma patients. The area under the receiver operating characteristic curve was used to determine the parameters indicating glaucomatous damage in the optic disc or retinal nerve fiber layer, which were used to establish additional subgroups of patients with preperimetric glaucoma. FDT and SWAP sensitivities were calculated for the patient subsets with structural damage and normal SAP. ResultsAt least 20% of the patients with preperimetric glaucoma demonstrated functional losses in FDT and SWAP. The more severe the structural damage, the greater the sensitivity for detecting glaucomatous visual field losses. ConclusionsFDT and SWAP detect functional losses in cases of suspected glaucoma before glaucomatous losses detected by SAP.

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.

Diagnostic ability of the Heidelberg retina tomograph, optical coherence tomograph, and scanning laser polarimeter in open-angle glaucoma.

PurposeTo compare the ability to discriminate between healthy and glaucomatous eyes of different criteria based on parameters from 3 optical imaging devices: Heidelberg retina tomograph (HRT-II), optical coherence tomograph (Stratus OCT 3000) and scanning laser polarimeter (GDx VCC). DesignCross-sectional study. ParticipantsA total of 139 eyes from 139 subjects were enrolled in this study and classified into 66 healthy subjects and 73 glaucomatous patients according to intraocular pressure and standard automated perimetry. MethodsAll the subjects underwent complete ophthalmic examination, including HRT-II, OCT, and GDx VCC evaluations. Main Outcome MeasuresSeveral parameters were obtained by these techniques and 8 diagnostic criteria were assessed. Receiver operating characteristics curves were plotted and compared among them, and sensitivity for specificity higher than 95% was calculated for every criterion. Agreement among the 3 technologies was assessed by means of Venn diagrams. ResultsThe best criteria discriminating between healthy and glaucomatous eyes were Moorfields regression analysis out of the 95% confidence interval (HRT-II), OCT retinal nerve fiber layer average thickness <77 μm, and nerve fiber indicator >37 (GDx VCC) with sensitivities of 85%, 66%, and 48%, with specificity higher than 95%. Sixty-six patients out of 73 were correctly identified by at least 1 of the devices and 30 were detected by the 3 of them. ConclusionsStructural criteria assessed by the optical imaging devices evaluated in this study are useful to discriminate glaucomatous damage.

Structure-function relationship depends on glaucoma severity

Background/aims: To determine the structure–function relationship throughout the different stages of glaucoma. Methods: Subjects: 228 controls and 1007 suspected, early, moderate, or advanced glaucomas. In controls, Pearson coefficient of variation (PCV) of standard automated perimetry mean sensitivity (SAP-MS) and global mean retinal nerve fibre layer thickness (RNFL, Heidelberg Retina Tomograph) were calculated. Piecewise linear regression was used to evaluate if the data were related better to two separate regression lines in all population. Results: PCV for SAP-MS and RNFL was 6.19% and 29.27%, respectively. For SAP-MS >22.42 dB (piecewise linear regression-obtained breakpoint, p<0.05), the logarithmic and linear relationships between SAP-MS and mean RNFL thickness were not different (r = 0.182, r = 0.185 respectively; p = 0.950). For SAP-MS <22.42 dB, the logarithmic and linear relationships between SAP-MS and mean RNFL thickness were not different (r = 0.353, r = 0.344 respectively; p = 0.884). Conclusion: The logarithmic and linear relationships between SAP-MS and mean RNFL thickness did not differ when individuals were stratified using the piecewise linear regression-obtained cut-off point. The curvilinear relationship between the morphological and perimetric results may be due to the wide variability in normal morphology and limitations in the dynamic range of the morphological tests in cases with moderate and severe defects.

Measuring hemoglobin levels in the optic nerve head: comparisons with other structural and functional parameters of glaucoma.

PURPOSE We evaluated and compared the ability of a new method for measuring hemoglobin (Hb) levels at the optic nerve head (ONH) to that of visual field evaluation, scanning laser ophthalmoscopy (HRT), scanning laser polarimetry (GDx), and optical coherence tomography (OCT) for diagnosing glaucoma. METHODS Healthy eyes (n = 102) and glaucomatous eyes (n = 101) underwent reliable Oculus Spark perimetry, and imaging with the HRT, GDx, and Cirrus OCT. In addition, ONH color images were acquired with a non-mydriatic fundus camera. The Laguna ON(h)E program then was used to calculate the Hb amount in each of 24 sectors of the ONH. Sensitivities at 95% fixed specificity, diagnostic agreement, and linear correlations between parameters with the best diagnostic ability were calculated. RESULTS The glaucoma discriminant function (GDF) of the Laguna program, evaluating Hb in the vertical intermediate sectors and center/periphery Hb amount slope, yielded an 89.1% sensitivity and 95.1% specificity, which was superior or similar to the other tests. The best GDF diagnostic agreement was for the OCT-vertical cup-to-disc (C/D) ratio (kappa = 0.772) and the final phase Spark pattern SD (kappa = 0.672). Hb levels correlated strongly with the Spark mean sensitivity (first phase 0.70, final phase 0.71). Hb also correlated well with the Reinhard OW Burk discriminant function of the HRT (0.56), nerve fiber indicator of GDx (-0.64), and vertical C/D ratio of OCT (0.71). CONCLUSIONS Hb levels evaluated by color analysis of ONH photographs had high reproducibility, a high sensitivity-specificity balance, and moderate to strong agreement with other structural and functional tests.

Predictive Value of Retrobulbar Blood Flow Velocities in Glaucoma Suspects

PURPOSE To determine whether retrobulbar blood flow (RBF) velocities are predictive of conversion to glaucoma. METHODS A total of 262 glaucoma suspects were prospectively selected. Participants had normal visual field, increased intraocular pressure, and glaucomatous optic disc appearance at baseline. Topographic analysis of the optic nerve head was performed using a confocal laser scanning ophthalmoscope and the blood flow velocity of retrobulbar vessels was measured by color Doppler imaging. Conversion to glaucoma was assessed according to the changes in the color-coded Moorfields Regression Analysis (MRA) classification of the confocal laser scanning system during a 48-month follow-up period. Survival curves and hazard ratios (HRs) for the association between RBF parameters and conversion to glaucoma were calculated. RESULTS End-diastolic velocity and mean velocity in the ophthalmic artery were reduced in subjects that converted to glaucoma based on MRA (36 individuals, 13.7%), while resistivity (RI) and pulsatility indices were increased in the same vessel. Patients with RI values lower than 0.75 in the ophthalmic artery had a survival rate (MRA-converters versus nonconverters) of 93.9%, whereas individuals with RI values greater than 0.75 had a survival rate of 81.7% (HR = 3.306; P = 0.002). CONCLUSIONS Abnormal RBF velocities measured by color Doppler ultrasound may be a risk factor for conversion to glaucoma. An RI value higher than 0.75 in the ophthalmic artery was associated with the development of glaucoma.

International vision requirements for driver licensing and disability pensions: using a milestone approach in characterization of progressive eye disease

Objective Low vision that causes forfeiture of driver’s licenses and collection of disability pension benefits can lead to negative psychosocial and economic consequences. The purpose of this study was to review the requirements for holding a driver’s license and rules for obtaining a disability pension due to low vision. Results highlight the possibility of using a milestone approach to describe progressive eye disease. Methods Government and research reports, websites, and journal articles were evaluated to review rules and requirements in Germany, Spain, Italy, France, the UK, and the US. Results Visual acuity limits are present in all driver’s license regulations. In most countries, the visual acuity limit is 0.5. Visual field limits are included in some driver’s license regulations. In Europe, binocular visual field requirements typically follow the European Union standard of ≥120°. In the US, the visual field requirements are typically between 110° and 140°. Some countries distinguish between being partially sighted and blind in the definition of legal blindness, and in others there is only one limit. Conclusions Loss of driving privileges could be used as a milestone to monitor progressive eye disease. Forfeiture could be standardized as a best-corrected visual acuity of <0.5 or visual field of <120°, which is consistent in most countries. However, requirements to receive disability pensions were too variable to standardize as milestones in progressive eye disease. Implementation of the World Health Organization criteria for low vision and blindness would help to establish better comparability between countries.

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.

Dexamethasone intravitreal implant as adjunct therapy for patients with wet age-related macular degeneration with incomplete response to ranibizumab

Purpose To evaluate the visual and anatomical outcomes of dexamethasone intravitreal implant (DXI; 700 μg, Ozurdex; Allergan, Irvine, California, USA) as adjunctive therapy for patients with refractory wet age-related macular degeneration (AMD). Methods Retrospective review of the medical records of seven patients (seven eyes) who initially responded well to intravitreal ranibizumab but subsequently developed persistent intra/sub-retinal fluid (IRF/SRF) and underwent a single injection of DXI, between May 2012 and May 2013. Two weeks after DXI, the patients continued with their monthly ranibizumab injections. Best corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (logMAR) and central retinal thickness (CRT) were recorded at baseline, 2 weeks, 6 weeks, 3 months and 6 months after DXI injection. Complications were recorded too. Results All patients had at least 24 months of ranibizumab treatment. Mean age was 81.5±5.8 years. At baseline, mean BCVA was 0.53±0.13 logMAR (20/70 Snellen) and mean CRT was 273.14±50.94 μm. BCVA did not change significantly after DXI over the follow-up period. However, all eyes had lost fewer than 0.3 logMAR units. Complete resolution of the persistent IRF/SRF was achieved in five eyes (71.4%) at 6 weeks, and remained stable at 3 months. Two weeks after DXI injection, the mean CRT diminished compared with baseline (248.28±31.8 µm; p=0.03) and the greatest reduction was observed at 3 months after DXI injection (241.5±36.6 µm; p=0.04). Progression of lens opacity was detected in one case (50% of phakic eyes). Retreatment with DXI was performed in two eyes. Conclusions DXI appears to be effective in vision stabilisation, decreasing IRF/SRF and improvement of CRT in eyes with refractory wet AMD.

Relationship between standard automated perimetry and retinal nerve fiber layer parameters obtained with optical coherence tomography.

PurposeTo determine the relationship between retinal nerve fiber layer (RNFL) parameters obtained using optical coherence tomography (OCT) and the outcome of standard automated perimetry (SAP) in normal, ocular hypertensive, glaucoma suspect, and glaucomatous patients. MethodsFour hundred twenty-three patients were enrolled in the study and classified based on basal intraocular pressure, optic nerve head morphology, and SAP results into 4 groups: 87 normal eyes, 192 ocular hypertensive eyes, 70 glaucoma suspects, and 74 glaucomatous eyes. In the different diagnostic groups, Pearson correlation coefficients were calculated between RNFL parameters and visual field indices, number of points altered at different probability levels, and threshold values at each SAP point. ResultsIn the normal and ocular hypertensive groups, very few mild correlations were found between the OCT parameters and SAP results. The strength and number of significant correlations was increased in the glaucoma suspect group. In the glaucoma group, the correlations were stronger, particularly between the inferior RNFL parameters and the superior hemifield. ConclusionsThe greater the visual field damage, the stronger the correlations between OCT and SAP. There was mild-to-moderate agreement between the structural and functional data assessed by OCT and SAP in glaucoma patients.