Progressive changes in the retinal nerve fiber layer in patients with multiple sclerosis.

PURPOSE: To quantify changes in the retinal nerve fiber layer (RNFL) of patients with multiple sclerosis (MS) over a 1-year time period and to compare the ability of noninvasive diagnostic imaging devices and visual evoked potentials (VEP) to detect axonal loss in these patients. METHODS: Eighty-one patients with MS underwent a complete ophthalmic examination that included assessment of visual acuity and color vision, refractive evaluation, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx), and measurement of VEP. All the patients were re-evaluated after a period of 12 months in order to quantify any change in the RNFL. Only one randomly chosen eye from each patient was included in the study. RESULTS: Statistically significant differences between the 2 examinations were recorded for the overall mean and inferior RNFL thickness and the macular volume, as assessed by OCT, as well as for the temporal-superior-nasal-inferior-temporal average standard deviation provided by GDx. The greatest differences were obtained for the mean RNFL thickness (90.46 microm vs 85.96 microm). Changes in the optic nerve were detected by structural measurements but not by functional assessments. CONCLUSIONS: Axonal loss in the optic nerve of patients with MS is greater than that expected in healthy subjects, regardless of the presence of a previous optic neuritis.

Ability of different optical imaging devices to discriminate between healthy and glaucomatous eyes.

We compared the ability to discriminate between healthy and glaucomatous eyes of three optical imaging devices in 140 eyes from 140 subjects. No statistically significant differences were found among the AUCs of these parameters. However, AUCs were significantly higher in OCT and HRT parameters than most of GDx VCC ones. Thus, structural parameters assessed by the optical imaging devices are useful to discriminate glaucomatous damage, but showed no significant difference among the best parameters from HRT, OCT or GDx VCC.

Comparative study of retinal nerve fiber layer thickness in normal eyes, ocular hypertensives, preperimetric glaucoma and glaucomatous subjects.

We assessed and compared the retinal nerve fiber layer (RNFL) thickness in normal eyes, ocular hypertensives, preperimetric glaucoma and glaucomatous subjects by means of optical coherence tomography in 449 eye. RNFL in glaucoma patients was significantly thinner than in normal subjects in every location evaluated. Use of optical coherence tomography detects glaucomatous RNFL losses in preperimetric glaucoma and can improve our ability to detect structural damage in clinical practice.

Ability of optical imaging devices to detect early structural damage in ocular hypertension.

We evaluated the ability of functional and structural technologies to detect early damage in ocular-hypertensive (OHT) eyes with normal standard automated perimetry (SAP) in 48 normal and 130 ocular-hypertensive subjects. We found that optical imaging devices may detect early damage in the RNFL and the optic nerve head in ocular-hypertensive eyes with no defect in SAP.

Comparison of the efficacy and safety of contact versus peribulbar anaesthesia in combined eye surgery.

PURPOSE: To compare the combined levels of comfort, the presence of complications and the results of phacotrabeculectomy surgery obtained with 2 different forms of anaesthesia: topical contact anaesthesia and peribulbar injected anaesthesia. PROCEDURES: In total, 120 consecutive patients undergoing phacotrabeculectomy were randomly assigned to each anaesthesia group. The patients were asked to rate their pain level on a 5-point scale at 3 time points during the procedure. Early and late surgical complications and clinical parameters of success were evaluated. RESULTS: Administration of contact anaesthesia was clearly associated with less pain than injection of peribulbar anaesthesia. The amount of pain or discomfort experienced during or following surgery did not differ between the patient groups. No long-term differences in the tensional results were observed between the groups of the study. CONCLUSION: The application of contact anaesthesia in the phacotrabeculectomy procedure provides a level of comfort and safety that is comparable to that achieved with peribulbar anaesthesia. Likewise, patients that received contact anaesthesia were as comfortable as patients that received the peribulbar injection of anaesthesia, not only during the immediate postoperative period, but also in terms of their tensional results and their visual acuity in the mid and long term.

Retinal nerve fiber layer evaluation in open-angle glaucoma. Optimum criteria for optical coherence tomography.

PURPOSE: To determine the optimum criteria for optical coherence tomography (OCT) to discriminate best between healthy and glaucomatous eyes. DESIGN: A prospective cross-sectional study. METHODS: In total, 164 eyes selected from clinical practice were included in this study. These were classified into 98 healthy and 66 glaucomatous eyes, depending on the intraocular pressure, appearance of the optic disc and standard automated perimetry results. Only 1 eye per subject was randomly included. The retinal nerve fiber layer (RNFL) was evaluated by means of OCT (Stratus OCT 3000). The sensitivity and specificity values of different diagnostic criteria (4 abnormal quadrants and 1-5 abnormal clock-hours) were calculated with different probability levels (p < 0.05 and p < 0.01). RESULTS: The criterion with the best sensitivity-specificity balance was the presence of >or=2 hour positions with an RNFL thickness outside of the 95% confidence interval (CI; sensitivity = 77.2%, specificity = 91.9%). For the 99% CI, the best criterion was the presence of at least 1 abnormal hour position (sensitivity = 71.2%, specificity = 91%). Regarding retinal quadrants, the presence of at least 1 quadrant with RNFL thickness outside of the CI was the criterion that best discriminated the existence of glaucomatous damage. CONCLUSIONS: The definition of diagnostic criteria based on OCT structural parameters may improve its diagnostic ability. The highest diagnostic ability was provided by the presence of at least 2 hour positions or RNFL average thickness outside the 95% CI.

Logistic regression analysis for early glaucoma diagnosis using optical coherence tomography.

OBJECTIVE: To determine and validate the diagnostic ability of a linear discriminant function (LDF) based on the retinal nerve fiber layer thickness at each of the 12 clock-hour positions obtained using optical coherence tomography for discriminating between healthy eyes and eyes with early glaucomatous visual field loss. METHODS: We prospectively selected 62 consecutive healthy individuals and 73 patients with open-angle glaucoma to calculate the LDF. Another independent prospective sample of 280 healthy eyes and 302 glaucomatous eyes was used to evaluate the diagnostic accuracy of the LDF. RESULTS: The proposed function was LDF = 15.584 - (12-o'clock segment thickness x 0.032) - (7-o'clock segment thickness x 0.041) - (3-o'clock segment thickness [nasal side] x 0.121). The greatest area under the receiver operating characteristic curve was observed for our LDF in both populations: 0.962 and 0.922. Our LDF and the average thickness yielded sensitivities of 74.5% and 67.8%, respectively, at a fixed specificity of 95%. CONCLUSIONS: The LDF increased the diagnostic ability of the isolated retinal nerve fiber layer thickness at the 12 clock-hour positions. Compared with optical coherence tomography-provided parameters, our LDF had the highest sensitivities at 85% and 95% fixed specificities to discriminate between healthy and early glaucomatous eyes.

Magnification characteristics of the Optical Coherence Tomograph STRATUS OCT 3000.

PURPOSE: To evaluate the magnification characteristics of an Optical Coherence Tomograph (STRATUS OCT 3000) used to measure optic disc size. METHODS: An eye model was designed, built and used to measure changes in the magnification of the Optical Coherence Tomograph (OCT) with variation in the axial length of the eye and OCT correction lenses. Theoretical calculations using ray-tracing were used to compare the experimental and theoretical results. RESULTS: OCT-performed fundus measurements have a magnification that depends on two factors: eye axial length and optical correction with the focusing dial of the OCT. Theoretical calculations showed that the size of the optic disc image for greater axial lengths of the eye model (myopic eye) was less than that for smaller axial lengths (hyperopic eye). The disc diameter measurements of the image obtained with the OCT did not agree with the real disc size. By focussing with the focusing dial of the OCT, the power of the optics can be varied from -12.0 D to +12.0 D and the image size is decreased for all axial lengths. The maximum variation of the disc area was 2.1%. Differences in area measured at intervals of 2.0 D after correcting the eye refraction for measurements with the OCT were equivalent to the repeatability error at that point. CONCLUSIONS: Our results confirm that any variation in the optical system of the eye, in the OCT, and/or in the distance between them, induces a change in the magnification of the tomograph images. These variations will affect the measurements of any of the structures in the retinal plane.

Effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% administered in the evening in glaucoma.

We evaluated the efficacy of fixed combination of 0.005% latanoprost and 0.5% timolol maleate administered once daily in the evening for treating glaucoma patients. This combination proved an effective alternative to achieve an additional intraocular pressure IOP lowering effect in patients treated with either drug alone and as an alterative in patients treated with unfixed combination of latanoprost and timolol and optimal IOP control.

Discriminating between normal and glaucoma-damaged eyes with the Heidelberg Retina Tomograph 3.

PURPOSE: To determine and validate the diagnostic ability of a linear discriminant function (LDF) based on global stereometric parameters obtained using the Heidelberg Retina Tomograph version 3 (HRT3) for discriminating between healthy eyes and eyes with glaucomatous visual field loss. DESIGN: Cross-sectional study. PARTICIPANTS: The authors prospectively selected 81 consecutive healthy subjects and 85 consecutive patients with open-angle glaucoma. Another prospective sample of 225 normal eyes and 210 glaucoma eyes was used to evaluate how well the LDF performed in another population. METHODS: Participants were divided into 2 groups depending on the results of standard automated perimetry and intraocular pressure. All participants underwent imaging of the optic nerve head with the HRT3. MAIN OUTCOME MEASURES: The LDF was calculated according to the stepwise logistic regression results of global optic nerve head parameters and glaucoma probability score numerical values. The diagnostic accuracy of the LDF and other parameters included in the software of the HRT3 was evaluated in another independent population. RESULTS: Based on the results of the stepwise binary logistic regression analysis, the function proposed was LDF = 8.23 - 8.00 x contour line modulation temporal superior + 9.41 x cup shape measure - 4.07 x rim area. The areas under the receiver operating characteristic curve were 0.875 for the LDF, 0.845 for the Frederick S. Mikelberg (FSM) discriminant function, and 0.838 for the Reinhard O. W. Burk (RB) discriminant function. There were no significant differences between these values. The LDF and the FSM and RB discriminant functions yielded sensitivities of 74.2%, 70.4%, and 67.6%, respectively, at a fixed specificity of 85%. CONCLUSIONS: Compared with the HRT-provided parameters, the proposed LDF exhibited higher diagnostic ability than most available analyses. The LDF had a better sensitivity and specificity balance than the FSM and RB discriminant functions, regardless of optic disc size.

Preperimetric glaucoma assessment with scanning laser polarimetry (GDx VCC): analysis of retinal nerve fiber layer by sectors.

PURPOSE: To evaluate the capability of the GDx VCC nerve fiber analyzer to detect preperimetric glaucoma across 12 retinal nerve fiber layer (RNFL) peripapillary sectors. METHODS: Data were obtained in a cross-sectional, hospital clinic-based study; 699 eyes from 699 glaucoma suspects were enrolled in this protocol. All subjects underwent ophthalmologic examination, static automated perimetry [Humphrey 24-2 Swedish interactive threshold algorithm (SITA) Standard], optic nerve stereoscopic photographs, red-free digital RNFL photographs and GDx VCC examination. Group S included 283 normal eyes and 39 preperimetric glaucoma eyes with RNFL superior or diffuse defects in the fiber layer photographs. Group I included 324 normal subjects and 24 with preperimetric glaucoma eyes with RNFL inferior or diffuse defects in fiber layer photographs. RESULTS: Mean values of the area under the curve (AUC) for receiver operating characteristic analysis for inferior average (Inf Avg), temporal-superior-nasal-inferior temporal average (TSNIT Avg), superior average (Sup Avg), and the nerve fiber indicator were significantly less in the eyes with RNFL defects than the control group compared with the AUC for thickness at hour 12 and at hour 6 calculated from the RNFL sector density. The AUC for receiver operating characteristic analysis of the new parameters improved by 12% with respect to the best GDx VCC standard values. CONCLUSIONS: Our results confirm that the 12 sector divisions of the GDx VCC have better diagnostic reliability in preperimetric glaucoma, and are able to improve the discrimination capability between normal and early damaged RNFLs.

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

PURPOSE: To assess the ability of frequency-doubling technology (FDT) perimetry and short-wavelength automated perimetry (SWAP) to detect glaucomatous damage in preperimetric glaucoma subjects. PARTICIPANTS: Two 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). METHODS: The 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. RESULTS: At 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. CONCLUSIONS: FDT and SWAP detect functional losses in cases of suspected glaucoma before glaucomatous losses detected by SAP.

Diagnostic ability of Heidelberg Retina Tomograph 3 classifications: glaucoma probability score versus Moorfields regression analysis.

PURPOSE: To evaluate the usefulness of the glaucoma probability score (GPS), which does not require manual outlining of the disc boundaries, and the Moorfields regression classification (MRA), which requires manual outlining of the disc boundaries, for discriminating between healthy and glaucomatous eyes, using the Heidelberg Retina Tomograph. DESIGN: Cross-sectional study. PARTICIPANTS: We prospectively selected 71 consecutive healthy subjects and 115 consecutive patients with open-angle glaucoma. METHODS: Participants were divided into 2 groups depending on the results of standard automated perimetry and intraocular pressure. All participants underwent imaging of the optic nerve head with the Heidelberg Retina Tomograph 3. All tests were performed within 1 month of each subject's date of enrollment into the study by examiners masked to the other findings. MAIN OUTCOME MEASURES: The sensitivity and specificity of all parameters of the MRA and GPS classifications were calculated. The diagnostic accuracy at different severities of glaucoma and optic disc sizes was also evaluated. Receiver operating characteristic curves were plotted for the GPS values. RESULTS: The MRA global classification had a sensitivity of 73.9% and a specificity of 91.5%. The GPS global classification had a sensitivity of 58.2% and a specificity of 94.4%. The GPS had slightly higher sensitivity and somewhat lower specificity than the MRA when there was mild damage indicated by visual field tests. The MRA had the best discrimination capability for moderate and severe glaucoma. Both the GPS and MRA had lower sensitivity and higher specificity for small optic discs (<1.7 mm2) compared with medium and large discs. CONCLUSIONS: In general, the diagnostic performance of the GPS was similar to that of the MRA. The diagnostic accuracy of both classifications depends on the optic disc size and the glaucoma severity.

Frequency-doubling technology: searching for the optimum diagnostic criteria for glaucoma.

PURPOSE: To determine the diagnostic criteria of perimetry using frequency-doubling technology (FDT) with the best possible sensitivity-specificity balance for glaucoma diagnosis. METHODS: A total of 92 healthy control subjects and 110 patients with varying degrees of glaucomatous visual field loss on standard automated perimetry (SAP) were used to obtain the best diagnostic criterion for the disease, by using screening C-20-1 and threshold C-20 strategies from original FDT perimetry. Another prospective sample of 52 normal eyes and 64 glaucoma eyes was used to test how well this optimum criterion performs in other populations. Receiver operating characteristic (ROC) curves were plotted for the number of altered points at each level of probability for the C-20-1 and threshold C-20 modes. In addition, ROC curves were calculated for the global indices of the threshold C-20 strategy. RESULTS: The best criterion for the C-20-1 strategy is the presence of one or more altered points with p < 1% (57.81% sensitivity and 100% specificity). The optimum criteria for glaucoma diagnosis for the threshold C-20 strategy are the presence of five or more altered points with p < 5% and/or two or more altered points with p < 2% and/or at least one altered point with p < 1% at any location (79.68% sensitivity and 94.2% specificity). CONCLUSIONS: By using the C-20-1 strategy, a p < 1% defect anywhere showed 100% specificity with the lowest test duration. The criteria proposed for the threshold C-20 algorithm presented a good sensitivity-specificity balance. The threshold C-20 test provides higher sensitivity than the C-20-1 strategy but takes about five times longer to perform.

Diagnostic ability of different tools for detection of glaucoma with confocal scanning laser tomography (Heidelberg Retina Tomograph II).

We evaluated the diagnostic ability of various diagnostic tools to detect glaucomatous damage in 101 normal eyes and 102 glaucomatous eyes. Mikelberg's linear discriminant function (LDF) obtained the best sensitivity followed by our own four formulas. With respect to specificity, Burk's LDF showed better results than Mikelberg's LDF and our formulae. Several Heidelberg retina tomograph analysis tools are useful to discriminate healthy from patients with glaucoma. Alternative tools based on normative databases derived from different autochthon populations add evidence needed to support their global use.

Multivariate analysis of structural parameters of the optic nerve head assessed by means of confocal scanning laser (Heidelberg Retina Tomograph II).

We evaluated the optic nerve head parameters measured by confocal scanning laser that discriminated between normal and glaucomatous subjects in 97 normal eyes and 94 glaucomatous eyes. Several different linear regression formulas can discriminate the presence of glaucomatous. The use of linear regression functions of HRT parameters elaborated from autochthon population around the world will add the amounts of evidence needed to support the global use of these functions.

Contact-topical plus intracameral lidocaine versus peribulbar anesthesia in combined surgery: a randomized clinical trial.

PURPOSE: To compare the efficiency and safety of contact-topical anesthesia versus peribulbar injection anesthesia for phacotrabeculectomy. MATERIALS AND METHODS: A total of 80 patients undergoing combined cataract and glaucoma surgery were randomly allocated to receive either contact or peribulbar anesthesia. No systemic sedatives were used in either group. Patients were asked to rate their pain level on a 5-point scale for 4 periods: during administration of the anesthetic agent; during surgery; immediately after surgery; and 24 hours postoperatively, while the surgeon recorded his subjective assessment of ease of surgery using a standardized template. The patients' general condition during surgery, as well as the results and short-term complications, were assessed. RESULTS: The injected anesthesia group showed higher rates of discomfort and pain, and 37 patients reported pain ranging from mild to severe during anesthetic administration. The difference between groups was statistically significant (P < 0.001). During surgery, there were no differences in vital signs, patients' subjective pain evaluation, or surgeon stress. We found no differences between pain rates after surgery. Complications included prolonged chemosis, and we also noted that conjunctival hemorrhage occurred more frequently in the peribulbar group than in the contact anesthesia group. CONCLUSION: Both anesthetic methods provide high levels of pain control without additional sedation during surgery. The use of contact-topical anesthesia avoids pain and reduces the possibility of complications during administration of anesthetics.

Contact versus peribulbar anaesthesia in trabeculectomy: a prospective randomized clinical study.

PURPOSE: To compare the pre-, intra- and postoperative pain scores and complication rates in trabeculectomy under contact-topical anaesthesia versus peribulbar injection anaesthesia. METHODS: A total of 100 patients selected to undergo primary trabeculectomy were randomly allocated to receive either contact or peribulbar anaesthesia. Patients were asked to rate their pain levels on a 5-point scale for four periods: during the administration of the anaesthetic agent, during surgery, immediately after surgery and 24 hours postoperatively. At the same time, the surgeon was asked to record his subjective assessment of the stress he himself had suffered during the course of the intervention. Surgical parameters, intra- and early postoperative complications were also evaluated. RESULTS: The difference between groups was statistically significant during anaesthetic administration. Six patients who received contact-topical anaesthesia reported mild discomfort during delivery of the anaesthetic agent, while 43 patients complained of mild to severe pain during the injection of bupivacaine (p < 0.001). Thirty-two patients in the contact anaesthesia group and 26 in the injected anaesthesia group reported no pain during surgery (p = 0.127). Only one patient in each group reported mild pain 30 min postoperatively. We found no differences between pain rates after surgery. Complications included prolonged chemosis and we also noted that conjunctival haemorrhage occurred more frequently in the peribulbar group than in the contact anaesthesia group (p = 0.012). CONCLUSION: Both anaesthetic methods provided high levels of pain control without additional sedation during surgery. The use of contact-topical anaesthesia reduces both pain and the possibility of complications during the administration of anaesthetics.

Predictive value of short-wavelength automated perimetry: a 3-year follow-up study.

PURPOSE: To determine whether structural changes in the retinal nerve fiber layer (RNFL) and functional abnormalities in short-wavelength automated perimetry (SWAP) can predict the onset of functional losses in standard automated perimetry patients suspected of having glaucoma. DESIGN: Prospective observational case series. PARTICIPANTS: A total of 160 eyes of ocular hypertensive subjects (intraocular pressure greater than 21 mmHg and normal standard automated perimetry) were included in the study. INTERVENTIONS: The subjects underwent RNFL photographic evaluation and SWAP. Standard automated perimetries were repeated after 3 years to evaluate glaucomatous losses. MAIN OUTCOME MEASURES: Onset of glaucomatous defects in conventional automated perimetry after 3 years of follow-up, with or without prior glaucomatous defects in RNFL and SWAP. RESULTS: At the beginning of the study, 77 eyes showed RNFL losses (48%), and 58 eyes showed abnormalities in SWAP (36%). After the 3-year follow-up period, 14 of 77 eyes with RNFL losses had standard automated perimetry abnormalities (predicting sensitivity 93%), whereas 11 of 58 eyes with abnormal SWAP had standard automated perimetry losses (73% sensitivity). CONCLUSIONS: RNFL and SWAP losses are signs of early glaucomatous damage and can predict functional losses in standard automated perimetry.