Applying a New Automated Perimetry Pattern Based on the Stimulus Distribution of the Multifocal ERG to Improve Structure-Function Investigation in Glaucoma.

PURPOSE: To validate a new automated perimetry pattern (mf103 pattern) for the investigation of retinal structure-function relationships in glaucoma in comparison to the standard G2 pattern and to relate either field's performance to optical coherence tomography (OCT). METHODS: Automated perimetry data from the mfERG103 pattern were compared with the standard G2 pattern in glaucoma patients (18) and controls (15). The results of both (mean defect (MD) and mean sensitivity (MS)) were compared with optical coherence tomography (OCT): retinal nerve fiber layer (RNFL) thickness, macular thickness (mT), and ganglion cell analysis (GCIPL). Nine patients were followed up after one year. RESULTS: G2 pattern and mf103 pattern did not differ significantly in MD or MS. The mf103 pattern associated significantly with more RNFL sectors in both MD and MS (p < 0.01 and p < 0.05, resp.). GCIPL thickness was not significantly associated with either SAP protocols. Both protocols remained comparable after one-year follow-up. CONCLUSIONS: G2 and mf103 pattern can both differentiate patients from controls with no significant difference in performance. RNFL thickness defects correlated better with mf103 than G2 with POAG. The mfERG-103 perimetry pattern can be used to establish structure-function correlations in glaucoma and may enable a more direct comparison with objective electrophysiological data.

Ganglion cell layer segmentation and the two-flash multifocal electroretinogram improve structure function analysis in early glaucoma.

PURPOSE: To improve structure-function analysis in primary open-angle glaucoma (POAG) by including the two-global flash multifocal electroretinogram (2F-mfERG) and macular ganglion cell layer segmentation. METHODS: Twenty-five glaucoma patients (six pre-perimetric (PPG), 19 POAG) and 16 controls underwent 2F-mfERG, optical coherence tomography (OCT), and standard automated perimetry (SAP). For 2F-mfERG, the root mean square was calculated for the focal flash response at 15-45 ms (DC) and the global flash responses at 45-75 ms (IC1) and 75-105 ms (IC2). For OCT, macular total thickness (mT) and ganglion cell-inner plexiform layer (GCIPL) thickness were analysed. Values from the central 10° and 15° of 2F-mfERG were compared to the corresponding areas from OCT and visual field. RESULTS: Both PPG and POAG had significantly lower mfERG responses in the central 10° and 15° than the control group. Of the glaucoma patients, 30.7% (three PPG, five POAG) showed central mfERG and GCIPL reduction without a SAP defect in the central 15 degrees. Four patients had a central SAP defect associated with a reduced GCIPL without any detectable dysfunction on mfERG. MfERG DC and IC2 were larger with increased mT (p ≤ 0.02), but GCIPL only related positively to IC2 (p = 0.027). SAP sensitivity also increased with thicker mT but not with GCIPL (p < 0.03 and p = 0.35). DC, IC2, and GCIPL could best differentiate glaucoma from control (AUC values: 0.897, 0.903, and 0.905). CONCLUSIONS: Structure function analysis in glaucoma can be improved when the GCIPL thickness as well as the 2F-mfERG is included as these measures complement information obtained by SAP.

Wavelet decomposition analysis in the two-flash multifocal ERG in early glaucoma: a comparison to ganglion cell analysis and visual field.

PURPOSE: To further improve analysis of the two-flash multifocal electroretinogram (2F-mfERG) in glaucoma in regard to structure-function analysis, using discrete wavelet transform (DWT) analysis. METHODS: Sixty subjects [35 controls and 25 primary open-angle glaucoma (POAG)] underwent 2F-mfERG. Responses were analyzed with the DWT. The DWT level that could best separate POAG from controls was compared to the root-mean-square (RMS) calculations previously used in the analysis of the 2F-mfERG. In a subgroup analysis, structure-function correlation was assessed between DWT, optical coherence tomography and automated perimetry (mf103 customized pattern) for the central 15°. RESULTS: Frequency level 4 of the wavelet variance analysis (144 Hz, WVA-144) was most sensitive (p < 0.003). It correlated positively with RMS but had a better AUC. Positive relations were found between visual field, WVA-144 and GCIPL thickness. The highest predictive factor for glaucoma diagnostic was seen in the GCIPL, but this improved further by adding the mean sensitivity and WVA-144. CONCLUSIONS: mfERG using WVA analysis improves glaucoma diagnosis, especially when combined with GCIPL and MS.

Comparison of Two Different OCT Systems: Retina Layer Segmentation and Impact on Structure-Function Analysis in Glaucoma.

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP). Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student's t-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP. Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 µm (SD 4.5) for MT and 9.8 µm (SD 5.4) for GCIPL (p < 0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p < 0.001). Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP.

A possible early sign of hydroxychloroquine macular toxicity.

PURPOSE: Hydroxychloroquine (HCQ) has a low risk of retinal toxicity which increases dramatically with a cumulative dose of >1000 g. Here we report a case of HCQ macular toxicity presentation in a young patient with a cumulative dose of 438 g. METHODS: A 15-year-old female started attending annual consultations for retinal toxicity screening in our clinic after 3 years of HCQ treatment for juvenile idiopathic dermatomyositis. She had been diagnosed at age 12 and had been on hydroxychloroquine 200 mg/day, cyclosporin 150 mg/day and vitamin D3 since. Screening consultations included: complete ophthalmologic examination, automated perimetry (AP, M Standard, Octopus 101, Haag-Streit), multifocal electroretinogram (VERIS 6.06™, FMSIII), optical coherence tomography (OCT, fast macular protocol, Cirrus SD-OCT, Carl Zeiss), fundus autofluorescence imaging (Spectralis OCT, Heidelberg Engineering Inc.) and color testing (Farnsworth-Panel-D-15). RESULTS: After 5 years of treatment, AP demonstrated reduced sensibility in only one extra-foveal point in each eye (p < 0.2). Even though other exams showed no alteration and the cumulative dose was only around 353 g, consultations were increased to every 6 months. After 2-year follow-up, that is, 7 years of HCQ, a bilateral paracentral macula thinning was evident on OCT, suggestive of bull's eye maculopathy. However, the retinal pigmented epithelium appeared intact and AP was completely normal in both eyes. Further evaluation with ganglion cell analysis (GCA = ganglion cell + inner plexiform layer, Cirrus SD-OCT, Carl Zeiss) showed a concentric thinning of this layer in the same area. Although daily and cumulative doses were still under the high toxicity risk parameters, HCQ was suspended. At a follow-up 1 year later, visual acuity was 20/16 without any further changes in OCT or on any other exam. CONCLUSIONS: This may be the first case report of insidious bull's eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

Suture Distension of Schlemm's Canal in Canaloplasty: An Anterior Segment Imaging Study.

Purpose. The object of this study was to investigate the role of the suture stent regarding its impact on reduction of intraocular pressure (IOP) in canaloplasty based on the distension of the inner wall of Schlemm's canal. Methods. Nineteen glaucoma patients who underwent canaloplasty with successful positioning of the tensioning suture were included. The measurements were analyzed using linear mixed models, with the means adjusted to IOP, age, cup-to-disc ratio, and time of follow-up. Results. Mean follow-up time was 27.6 months (SD 10.5). Mean intraocular pressure (IOP) was 24.6 mmHg (SD 5.29), 13.8 (SD 2.65), and 14.5 (SD 0.71) before surgery, at 12 months, and at 36 months after surgery, respectively. 57.9% of patients had no medication at last evaluation. Differences and variations of measurements between the devices over a time of 12 months were not significant (p = 0.15 to 0.98). Some angles of distension associated with the suture stent inside SC were predictive for IOP reduction (p < 0.03 to < 0.001), but not for final IOP (p = 0.64 to 0.96). Conclusion. The angles of the inner wall of Schlemm's canal generated by the suture stent were comparable between OCT and UBM and did not change significantly over time. There was a tendency towards a greater distension of Schlemm's canal, when the difference was larger between pre- and postoperative IOP, suggesting the tensioning suture may contribute to IOP reduction.

Update on Minimally Invasive Glaucoma Surgery (MIGS) and New Implants.

Traditional glaucoma surgery has been challenged by the advent of innovative techniques and new implants in the past few years. There is an increasing demand for safer glaucoma surgery offering patients a timely surgical solution in reducing intraocular pressure (IOP) and improving their quality of life. The new procedures and devices aim to lower IOP with a higher safety profile than fistulating surgery (trabeculectomy/drainage tubes) and are collectively termed "minimally invasive glaucoma surgery (MIGS)." The main advantage of MIGS is that they are nonpenetrating and/or bleb-independent procedures, thus avoiding the major complications of fistulating surgery related to blebs and hypotony. In this review, the clinical results of the latest techniques and devices are presented by their approach, ab interno (trabeculotomy, excimer laser trabeculotomy, trabecular microbypass, suprachoroidal shunt, and intracanalicular scaffold) and ab externo (canaloplasty, Stegmann Canal Expander, suprachoroidal Gold microshunt). The drawback of MIGS is that some of these procedures produce a limited IOP reduction compared to trabeculectomy. Currently, MIGS is performed in glaucoma patients with early to moderate disease and preferably in combination with cataract surgery.