Longitudinal Evaluation of Trifocal and Extended Depth of Focus Lenses Implantation using Standard Automated Perimetry Parameters

Purpose: To evaluate reliability and global indices parameters from standard automated perimetry (SAP) in normal eyes undergoing phacoemulsification cataract surgery with implantation of trifocal or extended depth of focus intraocular lens (IOL).Methods: Prospective comparative study. Comparison of trifocal IOL AcrySof IQ PanOptix® and extended depth of focus intraocular lens (EDOF) Tecnis Symfony® IOL. Patients underwent SAP pre- and postoperatively. Reliability indices (false negative rate - FN, false positive rate – FP), global indices (foveal sensitivity threshold, visual field index - VFI, standard pattern deviation – PSD, mean deviation MD) and test duration were analyzed.Results: A total of 23 eyes from 13 patients were in the trifocal IOL group and a total of 22 eyes from 14 patients were in the EDOF group The following results were obtained by analyzing pre- and postoperative SAP of EDOF IOL: the rate of change of FN was 1.95/1.41% (p=0.61); FP 1.64/1.27 (p=0.60); MD -1.60/-1.08dB (p=0.15); foveal sensitivity was 34.5/33.9dB (p=0.41); VFI 98.5/98.4% (p>0.99); PSD 1.85/1.86 (p=0.07); and for test duration 305.81/298.36s (p=0.35); all respectively. Analysis of pre- and postoperative parameters of trifocal IOL was: the rates of change of FN 1.22/1.83% (p=0.29); FP 1.65/1.48% (p=0.95); MD -1.55/-1.37dB (p=0.19) ; foveal sensitivity 33.9/34.9dB (p=0.47) ; VFI 98.6/98.3% (p=0.62); PSD 1.58/2.05 (p=0.02); and test duration 297.17/298.57s (p=0.87); all respectively. Conclusion: We identified a change in the PSD parameters in the trifocal IOL group. No other significant changes were identified in SAP parameters after implantation of trifocal AcrySof IQ PanOptix® and EDOF Tecnis Symfony® IOL. Longitudinal evaluation showed no changes in SAP after Trifocal and EDOF IOL implantation in normal subjects.

Elucidating Macular Structure-Function Correlations in Glaucoma

Correlation between structural data from optical coherence tomography (OCT) and functional data from the visual field (VF) may be suboptimal because of poor mapping of OCT measurement locations to VF test stimuli. We tested the hypothesis that stronger structure-function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3°x3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2°x2°) OCT grid was mapped to each of the 68 VF locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed and the maximum value used to generate vector maps. CMA yielded significantly higher structure-function correlations compared to LMA. Only 20% of the vectors with CMA and <5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of glaucomatous damage are more likely to affect the correlations rather than precise mapping of VF stimuli.

The Assessment of Morphological and Functional Changes in the Detection of the Initial Stage of Primary Glaucoma

Purpose — to study morphological and functional changes in the detection of primary glaucoma progression.Patients and methods. 128 patients (128 eyes, among them — 64 eyes with primary open angle glaucoma (POAG) and 64 with primary angle closure glaucoma (PACG)) with the initial MD of –6.0 dB were examined at the Ophthalmology Center of the FMBA of Russia from May 2016 to November 2019. The values of corneal-compensated IOP were also considered: minimal (IOPmin), peak (IOPmax) and its fluctuations (IOPfluct). The progression was measured using standard automated perimetry (SAP) and spectral-domain OCT (SD-OCT). During the observation period, each patient received the average of 8.42 ± 2.08 SAP and SD-OCT. Progressive thinning of the retinal nerve fiber layer (RNFL) and its ganglion cell complex (GCC) were evaluated using SD-OCT. If RNFL and/or GCC had a trend of significant (p < 0.05) thinning, the eye was classified as having the SD-OCT progression. The correlation between the rate of progression detected by SAP (ROP1) using thinning of RNFL (ROP2) and GCC (ROP3) with other clinical parameters was analyzed.Results and discussion. Glaucoma progression was detected in 73 eyes. While the isolated use of SAP did not allow detecting progression, it was possible to detect it in 39 % cases by SD-OCT. The combination of both methods allowed detecting progression in 57 %. In both forms, ROP1 correlated with IOPmin: in PACG r = 0.41, p = 0.023 and in POAG r = 0.43, p = 0.016. In PACG, ROP2 and ROP3 correlated with the foveal choroid thickness: r = 0.46, p = 0.019 and r = 0.47, p = 0.009, respectively. At the same time, ROP3 was associated with peak IOP (r = –0.402, p = 0.025); the correlation of peak IOP with its fluctuations amounted to 0.7 (p < 0.001).Conclusion. SD-OCT is more informative than SAP in determining the progression of the initial primary glaucoma. The combination of these two methods 1.5 times increases the possibility of detecting progression in comparison with the isolated use of SD-OCT. The choroid thickness, associated with the IOP fluctuations, plays an important role in the progression of PACG.

Prediction of glaucoma severity using parameters from the electroretinogram

Glaucoma is an optic neuropathy that results in the progressive loss of retinal ganglion cells (RGCs), which are known to exhibit functional changes prior to cell loss. The electroretinogram (ERG) is a method that enables an objective assessment of retinal function, and the photopic negative response (PhNR) has conventionally been used to provide a measure of RGC function. This study sought to examine if additional parameters from the ERG (amplitudes of the a-, b-, i-wave, as well the trough between the b- and i-wave), a multivariate adaptive regression splines (MARS; a non-linear) model and achromatic stimuli could better predict glaucoma severity in 103 eyes of 55 individuals with glaucoma. Glaucoma severity was determined using standard automated perimetry and optical coherence tomography imaging. ERGs targeting the PhNR were recorded with a chromatic (red-on-blue) and achromatic (white-on-white) stimulus with the same luminance. Linear and MARS models were fitted to predict glaucoma severity using the PhNR only or all ERG markers, derived from chromatic and achromatic stimuli. Use of all ERG markers predicted glaucoma severity significantly better than the PhNR alone (P ≤ 0.02), and the MARS performed better than linear models when using all markers (P = 0.01), but there was no significant difference between the achromatic and chromatic stimulus models. This study shows that there is more information present in the photopic ERG beyond the conventional PhNR measure in characterizing RGC function.

Monitoring for glaucoma progression with SAP, electroretinography (PERG and PhNR) and OCT

Purpose To investigate the value of pattern electroretinography (PERG) and photopic negative response (PhNR) in monitoring glaucoma compared to standard clinical tests (standard automated perimetry (SAP) and clinical optic disc assessment) and structural measurements using spectral-domain OCT. Methods A prospective study included 32 subjects (32 eyes) with ocular hypertension, suspect or early glaucoma monitored for progression with clinical examination, SAP, PERG, PhNR and OCT for at least 4 years. Progression was defined clinically by the documented change of the optic disc and/or significant visual field progression (EyeSuite™ trend analysis). One eye per patient was included in the analysis. Results During the follow-up, 13 eyes (40.6%) showed progression, whereas 19 remained stable. In the progressing group, all parameters showed significant worsening over time, except for the PhNR, whereas in the stable group only the OCT parameters showed a significant decrease at the last visit. The trend of change over time using linear regression was steepest for the OCT parameters. At baseline, only the ganglion cell complex (GCC) and peripapillary retinal nerve fibre (pRNFL) thicknesses significantly discriminated between the stable and progressing eyes with the area under the ROC curve of 0.72 and 0.71, respectively. The inter-session variability for the first two visits in the stable group was lower for OCT (% limits of agreement within ± 17.4% of the mean for pRNFL and ± 3.6% for the GCC thicknesses) than for ERG measures (within ± 35.9% of the mean for PERG N95 and ± 59.9% for PhNR). The coefficient of variation for repeated measurements in the stable group was 11.9% for PERG N95 and 23.6% for the PhNR, while it was considerably lower for all OCT measures (5.6% for pRNFL and 1.7% for GCC thicknesses). Conclusions Although PERG and PhNR are sensitive for early detection of glaucomatous damage, they have limited usefulness in monitoring glaucoma progression in clinical practice, mainly due to high inter-session variability. On the contrary, OCT measures show low inter-session variability and might have a predicting value for early discrimination of progressing cases.

Optic Nerve Head Hemoglobin Levels in Glaucoma: A Structural and Functional Correlation Study

Purpose. To investigate structural and functional correlations in glaucoma patients using optic nerve head hemoglobin (ONH Hb) measurements as determined by automated colorimetric analysis of conventional retinography. Methods. We prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (standard automated perimetry, SAP), color fundus imaging (mydriatic retinography), and peripapillary retinal nerve fiber layer (pRNFL) assessment through spectral-domain optical coherence tomography (SD-OCT). Software Laguna ONhE was used to estimate the amount of ONH Hb and to determine the glaucoma discriminant function (GDF) index. Scatter plots were constructed, and regression analysis was used to investigate the correlations between GDF, average pRNFL thickness, and VF mean deviation (VFMD) index values. A secondary analysis was performed to compare each parameter between three different glaucoma groups divided according to VFMD values (mild, >−6 dB; moderate, −6 to −12 dB; and advanced, <−12 dB). Results. One hundred ninety-six eyes from 123 participants (69 with glaucoma and 54 controls) were enrolled. Overall, all parameters evaluated differed significantly between glaucomatous and control eyes ( p ≤ 0.001 ). The comparison of each parameter according to groups of disease stages revealed significant differences between controls and each of the glaucomatous groups ( p < 0.001 ). More pronounced changes in GDF values were observed in early disease stages. We found significant nonlinear correlations between GDF and VFMD values (R2 = 0.295, p < 0.001 ) and between pRNFL thickness and VFMD (R2 = 0.598, p < 0.001 ). A linear correlation was found between GDF and pRNFL thickness values (R2 = 0.195, p < 0.001 ). Conclusion. Our results showed significant associations between ONH Hb values and both structural and functional damage in glaucoma obtained by SD-OCT and SAP, respectively. The nonlinear correlation we found and the GDF behavior along different disease stages suggest that ONH Hb levels’ reduction may precede visual function changes in early glaucoma stages.

Patients Prefer a Virtual Reality Approach Over a Similarly Performing Screen-Based Approach for Continuous Oculomotor-Based Screening of Glaucomatous and Neuro-Ophthalmological Visual Field Defects

Standard automated perimetry (SAP) is the gold standard for evaluating the presence of visual field defects (VFDs). Nevertheless, it has requirements such as prolonged attention, stable fixation, and a need for a motor response that limit application in various patient groups. Therefore, a novel approach using eye movements (EMs) – as a complementary technique to SAP – was developed and tested in clinical settings by our group. However, the original method uses a screen-based eye-tracker which still requires participants to keep their chin and head stable. Virtual reality (VR) has shown much promise in ophthalmic diagnostics – especially in terms of freedom of head movement and precise control over experimental settings, besides being portable. In this study, we set out to see if patients can be screened for VFDs based on their EM in a VR-based framework and if they are comparable to the screen-based eyetracker. Moreover, we wanted to know if this framework can provide an effective and enjoyable user experience (UX) compared to our previous approach and the conventional SAP. Therefore, we first modified our method and implemented it on a VR head-mounted device with built-in eye tracking. Subsequently, 15 controls naïve to SAP, 15 patients with a neuro-ophthalmological disorder, and 15 glaucoma patients performed three tasks in a counterbalanced manner: (1) a visual tracking task on the VR headset while their EM was recorded, (2) the preceding tracking task but on a conventional screen-based eye tracker, and (3) SAP. We then quantified the spatio-temporal properties (STP) of the EM of each group using a cross-correlogram analysis. Finally, we evaluated the human–computer interaction (HCI) aspects of the participants in the three methods using a user-experience questionnaire. We find that: (1) the VR framework can distinguish the participants according to their oculomotor characteristics; (2) the STP of the VR framework are similar to those from the screen-based eye tracker; and (3) participants from all the groups found the VR-screening test to be the most attractive. Thus, we conclude that the EM-based approach implemented in VR can be a user-friendly and portable companion to complement existing perimetric techniques in ophthalmic clinics.

Global Glaucoma Staging System (GGSS): A New Method to Simultaneously Assess the Severity of Both Functional and Structural Damage in Glaucoma

Background: The classification of damage in glaucoma is usually based either on visual field or optical coherent tomography (OCT) assessment. No currently available method is able to simultaneously categorize functional and structural damage. Material and Methods: In this study, 283 patients with chronic open-angle glaucoma (OAG) at different stages and 67 healthy subjects were tested with both standard automated perimetry and spectral domain OCT for retinal nerve fiber layer (RNFL) assessment. The visual field data were classified using the Glaucoma Staging System 2, whereas OCT results were processed with the OCT Glaucoma Staging System. These data were used to create a new staging system (global glaucoma staging system, GGSS), in which the severity of visual field and RNFL damage is reported on the Y and X axis, respectively. The GGSS was tested in a different sample of 147 patients with manifest OAG, 56 with preperimetric glaucoma and 43 normal subjects. A six-stage clinical classification, based on the analysis of visual fields and optic disc appearance, was used as gold standard. Results: The GGSS was able to correctly classify in the same stage or within the immediately adjacent stages 145 cases on 147 (98.6%). Fifty-four preperimetric cases (96.4%) were classified as borderline or abnormal (Stage 1 or 2). Here, 41 normal eyes out of 43 were correctly classified as Stage 0, with a specificity of 95.3%. Conclusions: Preliminary results from this study are encouraging and suggest that the new GGSS is able to provide information concerning the severity of structural and functional damage in an integrated manner.

Mapping Visual Field Defects With fMRI – Impact of Approach and Experimental Conditions

Current initiatives to restore vision emphasize the need for objective assessments of visual field (VF) defects as pursued with functional magnetic resonance imaging (fMRI) approaches. Here, we compared population receptive field (pRF) mapping-based VF reconstructions to an fMRI method that uses more robust visual stimulation (on-off block design) in combination with individualized anatomy-driven retinotopic atlas-information (atlas-based VF). We investigated participants with sizable peripheral VF-deficits due to advanced glaucoma (n = 4) or retinitis pigmentosa (RP; n = 2) and controls (n = 6) with simulated scotoma. We obtained (1) standard automated perimetry (SAP) data as reference VFs and 3T fMRI data for (2) pRF-mapping [8-direction bar stimulus, fixation color change task] and (3) block-design full-field stimulation [8-direction drifting contrast patterns during (a) passive viewing (PV) and (b) one-back-task (OBT; reporting successions of identical motion directions) to probe the impact of previously reported task-related unspecific visual cortex activations]. Correspondence measures between the SAP and fMRI-based VFs were accuracy, assisted by sensitivity and specificity. We found an accuracy of pRF-based VF from V1 in patients [median: 0.62] that was similar to previous reports and increased by adding V2 and V3 to the analysis [0.74]. In comparison to the pRF-based VF, equivalent accuracies were obtained for the atlas-based VF for both PV [0.67] and, unexpectedly, the OBT [0.59], where, however, unspecific cortical activations were reflected by a reduction in sensitivity [0.71 (PV) and 0.35 (OBT)]. In conclusion, in patients with peripheral VF-defects, we demonstrate that previous fMRI procedures to obtain VF-estimates might be enhanced by: (1) pooling V1-V3 to enhance accuracy; (2) reporting sensitivity and specificity measures to increase transparency of the VF-reconstruction metric; (3) applying atlas-based procedures, if pRF-based VFs are not available or difficult to obtain; and (4) giving, counter-intuitively, preference to PV. These findings are expected to provide guidance to overcome current limitations of translating fMRI-based methods to a clinical work-up.