Artificial Intelligence-Guided Endpoint Selection for Neuroprotection Trials in Glaucoma.

Purpose:To investigate the effect of cataract surgery and yellow-tinted intraocular lens (IOLs) implantation on perimetry indices of short-wavelength automated perimetry (SWAP) and standard automated perimetry (SAP) testing in patients with coexisting cataract and glaucoma.Materials and Methods:In this prospective comparative case series, phacoemulsification with implantation of yellow-tinted Acrysof Natural IOL was performed in 16 eyes of 16 patients with visually significant cataract (best-corrected visual acuity (VA) better than 20/120) and mild to moderate glaucoma. Pre- and postoperative values for VA and for perimetry indices including mean deviation (MD), pattern standard deviation (PSD), and foveal threshold (FT) from both SAP and SWAP testing were compared.Results:Postoperative VA improved significantly after cataract surgery and yellow-tinted IOL implantation (P < 0.001). After cataract extraction and IOL implantation, MD and FT on SWAP testing improved significantly (P = 0.001); however, there was no statistically significant change with SAP testing between the pre- and postoperative perimetry indices. There was no statistically significant change in PSD with either SAP or SWAP testing postoperatively. The differences between pre- and postoperative values for all perimetry indices under study were not significant when comparing SAP with SWAP tests, except for MD which had improved statistically significantly in SWAP testing (P = 0.03).Conclusions:In mild to moderate glaucoma patients with cataracts, the perimetry indices of SWAP testing improved after phacoemulsification and yellow-tinted IOL implantation. This suggests that the yellow-tinted IOLs have less effect on SWAP testing than visually significant cataracts.

PurposeTo 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.MethodsTwenty-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.ResultsBoth 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).ConclusionsStructure 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.

Comparison of Short- And Long-Term Variability in Standard Perimetry and Spectral Domain Optical Coherence Tomography in Glaucoma

Inefficacy of Longitudinal Cup-to-Disc Ratio Measurements in Identifying Glaucoma Progression.

Dear Editor, We read with interest the article titled “Evidence-based approach to glaucoma management” by Garudadri et al.[1] Standard automated perimetry (SAP) is the current standard in glaucoma diagnosis, but 20-40% retinal ganglion cells could be lost before a visual field defect could be picked up by SAP. The reported sensitivity and specificity of image technologies and their agreement with each other are far from ideal. Brain and eye have adaptive strategies to compensate scotoma. Safran and Landis[2] in a review article described the effects of plasticity in the adult visual cortex. Plasticity plays a crucial role in recovery from damage to the visual system. Cortical remapping generates a filling-in of visual field defects. Cortical rearrangement following lesions in the visual pathways helps to compensate for gaps in perception. Filling-in is a major cause of failure of patients with simple chronic glaucoma to recognize their visual defects at an early stage. Qing et al.,[3] have documented that more affected the visual field (SAP), the less affected the functional magnetic resonance image response. This phenomenon may imply a replasticity or a compensatory mechanism of the visual pathway. Peripheral scotoma may have a potentiating effect on the central reserved visual field. Decreased retina input may result in replasticity of the cortical neurons and enhance the information processing and integrity ability of the visual cortex. Measurement of blue chromatic thresholds in the macular region might make it possible to detect functional damage due to glaucoma prior to morphological changes of the optic nerve head of glaucoma patients. Probably a combination of decreased peripheral sensitivity with increased central retinal sensitivity may be suggestive of early glaucoma. Alzheimer's disease and Parkinson's disease cause retinal nerve fiber loss (RNFL). Evidence shows that microtubules in nerve fiber bundles are the major contributors for retinal nerve fiber layer birefringence, and microtubules are expected to disappear after the ganglion cells die. It remains to be clarified whether the time lag between cell death and microtubules disappearance or other subcellular changes differ between primary open angle glaucoma (POAG) and primary angle closure glaucoma. Preferred retinal locus (PRL) and oculomotor re-referencing are adaptive strategies of eye to compensate scotoma.[4] A PRL can be defined as a discrete retinal area that contains the center of target image for greater than 20% of a fixation interval. Oculomotor re-referencing is a phenomenon seen in patients who describe themselves as looking straight ahead when they are fixating with PRL (i.e., when the eye is not in the primary position). Fixation instability is a feature documented in early and moderate POAG.[5] This may be considered as an evidence for ocular adaptive strategy to compensate scotoma because eccentric fixation induces instability. Probably a combination of RNFL and recent onset fixation instability may improve sensitivity and specificity of image technologies. In conclusion, we agree with the authors advice that good history taking, proper clinical examination, documentation of details, supplemented with appropriate investigations, counseling, and proper follow-up enhance the care of the patient and family.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study

To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. The RGC+IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71-0.74). Agreement was worse (0.53-0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. In the central 7.2°, local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement.

To investigate achromatic temporal summation under the conditions of standard automated perimetry (SAP), using a Goldmann III (GIII) stimulus and a stimulus scaled to the local area of complete spatial summation (Ricco's area) in open-angle glaucoma (OAG) patients and healthy age-similar control participants. Twenty patients with OAG (mean age, 63 years; mean MD, -3.3 dB) and 15 healthy controls (mean age, 64 years) were recruited. Contrast thresholds were measured for seven stimulus durations (1-24 frames, 1.8-191.9 ms) using a near-GIII stimulus (0.48° diameter) and stimuli scaled to the local Ricco's area, in four oblique meridians at 8.8° eccentricity in the visual field. The upper limit of complete temporal summation (critical duration) was estimated using iterative two-phase regression analysis. Median critical duration values were significantly longer (P < 0.05) in the OAG group for the near-GIII (107.2 ms; interquartile range [IQR], 38.0-190.5) and Ricco's area-scaled (83.2 ms, 41.7-151.4) stimuli, compared to those in healthy subjects (near-GIII, 34.7 ms; 18.2-47.9; Ricco's area-scaled, 49.0 ms; 25.1-64.6). The greatest difference in contrast thresholds between healthy and OAG subjects (i.e., disease signal) was found when stimuli were scaled to Ricco's area and shorter than or equal to the critical duration in healthy observers. Temporal summation is altered in glaucoma. The stimulus duration and area of conventional SAP may be suboptimal for identifying early functional damage. Simultaneously modulating stimulus duration, area, and luminance during the examination may improve the diagnostic capability of SAP and expand the dynamic range of current instruments.

To investigate visual field (VF) progression patterns in an Asian population with glaucoma and assess how age, disease severity, and a universal health coverage system (Taiwan's National Health Insurance, NHI) jointly influence long-term outcomes. This 10-year retrospective study (2013-2022) at a tertiary referral center included patients with ≥ 4 reliable standard automated perimetry (SAP) tests using 24-2 and 30-2 Swedish Interactive Threshold Algorithm strategies. Patients were stratified by age (< 40, 40-65, > 65) and disease severity (mild, moderate, severe, advanced). VF progression was analyzed using linear mixed models. A total of 9,901 SAP tests from 1,841 patients (mean age: 47.17 ± 16.23years) were analyzed. The overall VF progression rate was -0.044 ± 0.956dB/year. The observed progression in our cohort appeared slower, which may be associated with earlier diagnosis and consistent care under NHI. However, direct comparisons with Western cohorts should be interpreted cautiously due to differences in glaucoma subtypes and patient demographics. Significant progression was seen in mild to severe cases, but not in advanced glaucoma. Patients over 65 with mild disease showed accelerated decline, suggesting an age-severity interaction. As the first large-scale, decade-long study of VF progression in an Asian cohort under universal health coverage, our findings reveal a synergistic interaction between age and disease severity, with elderly patients-especially those with mild disease-facing accelerated decline. The slower progression observed under NHI suggests that equitable, accessible care may help mitigate long-term visual loss. These results underscore the importance of early detection, tailored intervention, and policy support to improve outcomes in aging glaucoma Asian populations. What is known Visual field (VF) progression is a critical indicator in glaucoma care and has been extensively studied in Western populations. Disease severity and aging are established risk factors for glaucoma progression. What is new This is the first large-scale, real-world longitudinal analysis of VF progression in an Asian glaucoma cohort under universal health coverage over a 10-year span. In our cohort, patients were relatively younger at diagnosis and exhibited slower VF deterioration, which may reflect the influence of Taiwan's National Health Insurance system in facilitating early detection and continuous care. Cross-population comparisons should be interpreted with caution given differences in glaucoma subtypes and demographics. Elderly patients with mild glaucoma exhibited unexpectedly rapid VF decline, suggesting a need for more aggressive early management.

Objective: To study the alteration of the optic radiations in patients with primary open-angle glaucoma (POAG) by diffusion tensor imaging (DTI) and tractography, and to reveal the correlation between the DTI derived parameters and the severity of the disease. Methods: A total of 24 patients with POAG and 20 age- and gender-matched healthy controls were enrolled in this study from January 2011 to June 2013.All subjects underwent ophthalmoscopy, standard automatic perimetry, intraocular pressure measurement and MRI scanning.All the eyes of POAG patients were evaluated by Hodapp-Anderson-Parrish (HAP) system.Then the stages of bilateral eyes were added together to evaluate the disease severity.Tractography was used to measure the fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the optic radiations of these subjects.The results of the two groups were compared.Partial correlation was then used to reveal the correlation between these derived DTI parameters and the severity of POAG. Results: Compared with health controls, POAG patients showed significant decreased FA (t=-3.299, P=0.002) and AD (t=-2.485, P=0.013), increased RD (t=2.365, P=0.018) in optic radiation .The alteration of MD was not significant (t=0.719, P=0.454). Mean FA values of the optic radiations were negatively correlated with POAG stages (r=-0.643, P= 0.001), while mean RD values (r=0.570, P= 0.004) and mean MD values (r= 0.448, P= 0.028) were positively correlated with POAG stages.No correlation between AD values and severity of POAG was found. Conclusion: In the optic radiations of POAG patients, the FA values and AD values decrease, while RD values increase, indicating the fiber integrity changes.The alterations of FA, RD and MD are correlated with disease severity.

Longitudinal changes in the visual field and optic disc in glaucoma

To evaluate the performance of frequency doubling technology (FDT) perimetry in open-angle glaucoma eyes with hemifield visual field damage and to compare it between open-angle glaucoma with high pressure [high-tension glaucoma (HTG)] and those with normal pressure [normal-tension glaucoma (NTG)] groups. FDT perimetry with the N-30 full threshold protocol and standard automated perimetry (SAP) using the Humphrey Field Analyzer with the 30-2 full threshold protocol were performed in 20 eyes of 20 HTG patients and 36 eyes of 36 NTG patients with visual field damage confirmed with SAP in only one hemifield. There was no significant difference in demographics, the Heidelberg Retina Tomography indices, and the Humphrey Field Analyzer indices between HTG and NTG groups. Regarding the FDT perimetry results, mean deviation in the global field (P=0.009) and mean sensitivity in the SAP-spared (P=0.001) and SAP-impaired (P=0.011) hemifields were lower; the numbers of FDT abnormal test points (probability of abnormality <5%) in the SAP-spared hemifield were significantly greater (P=0.005) in HTG than in NTG groups. Eyes in which FDT results of the SAP-spared hemifield were judged as abnormal was more frequent in HTG groups (P=0.007). The performance of FDT perimetry to detect early or preperimetric glaucomatous functional changes should be different between HTG and NTG eyes.

To establish a map relating visual field (VF) test points to corresponding areas of the retinal nerve fiber layer (RNFL) measured with optical coherence tomography (OCT) in patients with glaucomatous optic neuropathy. One hundred four consecutive subjects with open-angle glaucoma were prospectively selected. All subjects underwent standard automated perimetry (SAP) and imaging with OCT. Factor analyses of the mean thresholds for the SAP test points were performed, independently for each hemifield, to define regions of related points. Pearson correlations were then calculated between the VF regions and peripapillary RNFL thickness measured with OCT at each of the 12 clock-hour positions. A map relating the VF regions to the OCT sectors was plotted based on the strongest correlations between both techniques. Factor analysis distributed the VF points into five VF regions for each hemifield. A slightly asymmetric distribution of VF regions was obtained for the upper and lower points, with respect to the horizontal meridian. Mild to moderate correlations were observed between the VF regions and RNFL thickness. The superior VF regions and RNFL segments correlated most strongly at the 6- and 7-o'clock positions (r = 0.4-0.5). There was a moderate association between the VF regions and the RNFL thickness in patients with glaucomatous optic neuropathy, as measured by OCT. Within sectors of the RNFL, there was some overlap in the representation of the VF regions. The map obtained validates previously reported clinical findings and contributes to a better understanding of the relationship between structure and function in patients with glaucoma.

Glaucoma remains one of the leading causes of acquired blindness worldwide (Thylefors & Negrel, 1994; Quigley & Broman, 2006). Open-angle glaucoma (OAG) including primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG), is the most common type of glaucoma and is just a representative chronic disease such as hyptertension and diabetes mellitus (Schwartz & Quigley, 2008; Quigley, 2011). Because the ultimate goal of glaucoma treatment is to maintain long-term visual function, glaucomatous patients require essentially lifelong follow-up. Thus, we need an approach to glaucoma management that considers patients’ present visual functions as well as their future prognosis. The pathogenesis of glaucomatous optic neuropathy as well as the details of its long-term progression have not beeen clered yet. Many clinical trials have confirmed the importance of intraocular pressure (IOP) in the development and progression of OAG (Kass et al., 2002; Gordon et al, 2002; Heijl et al. 2002; 2003; Leske et al, 1999; 2003; Collaborative normaltension glaucoma study group, 1998; 2001; Anderson et al, 2003; The AGIS Investigators, 1994; 2000; Katz, 1999; Musch et al, 2009; Parrish et al, 2009; Chauhan et al, 2008). These studies have shown that lowering IOP reduces the risk of developing OAG and slows its progression. The aim of current glaucoma treatment approaches is to maintain patients’ visual function for as long as possible by reducing IOP. In addition to visual function, of course, we monitor patients’ IOP, optic discs, and retinal changes. Since preservation of visual fields is the final outcome in glaucoma management, ongoing evaluation of patients’ visual fields must be the most important activity in clinical practice. Recently, the morphological evaluation of optic disc cupping, retinal nerve fiber layer defects, and the retinal ganglion cell complex by imaging systems such as optical coherence tomography (OCT) has become popular (Wollstein et al, 2005; Tan O et al, 2009). After all these systems provide only the ability to reliably and safely detect or predict glaucoma progression beside monitering visual field and visual acuity (Hood & Kordon, 2007; Harwerth et al, 2010; Parrish et al, 2009). Standard automated perimetry (SAP) is used to examine and evaluate visual fields, but the technique is difficult to perform and have still has many problems. Furthermore, there is

Aim: to determine a level of "target" intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG), depending on the disease stage. Patients and Methods: a final protocol of a multicenter scientific analytical selective combined study conducted in 6 countries (Russia, China, Belarus, Serbia, Slovakia and Uzbekistan) at 25 clinical centers included data from 269 patients. The stage of glaucoma was confirmed by ophthalmoscopy and/or fundus photography and/or optical coherence tomography and/or Heidelberg tomography, and standard automatic perimetry (SAP). Visual acuity was examined, clinical refraction was determined, a tonometric level of IOP was measured (Maklakov tonometry with a 10 g load, Caucasian population), and Goldman tonometry results (Asian population) were evaluated. Results: at diagnosis, patients with NTG were several years younger than those with primary open-angle glaucoma (POAG). The greatest increase in glaucoma progression was reported in patients with the advanced disease (+91.4%), while a number of patients with stages I and II decreased by 5.5% and 23.4%, respectively. In patients with mild NTG (stage I), IOP level reduced by 19.9% and 16.6% from the initial values when measured by Maklakov and by Goldman methods, respectively. In patients with stages II и III, the parameter values decreased by 17.1% and 9.4% (on average, by 14.1%), as well as by 21.9% and 9.3% (on average, by 15.3%), respectively. Only among patients with advanced NTG, the progression rate was approximately 7 times higher in individuals with the appropriate family history (p=0,016; U=2,416). Conclusion: regardless of the disease stage, the lower an initial IOP level, the less it can be reduced towards the final examination. During the entire follow-up period, an average decrease in the IOP level was 16.5% regardless of the NTG stage. Due to the treatment provided, IOP in NTG patients was on average 2–4 mm Hg lower than that in individuals with POAG. Thus, current guidelines to determine "target" values of the parameter in this group of patients should be amended. KEYWORDS: normal-tension glaucoma, "target" intraocular pressure, glaucoma progression, tonometry. FOR CITATION: Egorov E.A., Kuroyedov A.V., Zavadskiy P.Ch., Vitkov А.А., Bakunina N.A., Baryshnikova D.A., Bulakh I.A., Zvereva O.G., Zubasheva S.A., Galimova A.B., Gaponko O.V., Getmanova A.M., Gusarevich A.A., Korelina V.E., Lanin S.N., Stepanova E.A., Chernyakova T.V., Shakhalova A.P., Razhko Yu.I., Yuan H., Sun X., Wu L., Bozic М., Ferkovа S.L., Zakhidov A.B. Target intraocular pressure level in patients with different stages of low tension glaucoma. Russian Journal of Clinical Ophthalmology. 2025;25(1):9–19 (in Russ.). DOI: 10.32364/2311- 7729-2025-25-1-2