Advanced Stages Of Primary Open-angle Glaucoma Research Articles

The potential of a fixed combination of brimonidine and timolol in achieving safe intraocular pressure levels after micropulse laser cyclophotocoagulation

PURPOSE. To evaluate the clinical effectiveness and safety of using a fixed combination — hypotensive drug Brimonidine Duo (brimonidine tartrate 2 mg/mL + timolol maleate 5 mg/mL) to reduce intraocular pressure in patients with advanced stages of primary open-angle glaucoma (POAG) in cases when achieving target pressure failed after laser micropulse transcleral diode laser cyclophotocoagulation (mCPC).METHODS. MCPC was performed with individually chosen parameters in 100 patients (104 eyes) aged 35 to 86 with POAG, of them 54.17% were men and 45.83% were women. The follow-up period lasted 3 months, the results were evaluated on the 1st, 7th and 14th days, then after 1 and 3 months. In 23.08% of cases (24 patients) subjects were prescribed antihypertensive combination drug Brimayza Duo due to intraocular pressure (IOP) remaining uncompensated.RESULTS. The average IOP level after 7 days was 23.54± 4.8 mm Hg. After 3 months, IOP values were 18.11±2.04 mm Hg, which is 4–5 mm Hg lower than in the early postoperative period. After 30 days of follow-up, an additional antihypertensive drug Latanoprost 0.005% was added for 5 patients (20.83%). Repeated surgery was recommended and performed in 4 patients (16.67%), of which 1 patient underwent surgical intervention of the penetrating type, 3 patients underwent repeat mCPC with individually chosen parameters.CONCLUSION. MCPC is a safe and effective tool for reducing intraocular pressure in patients with advanced stages of POAG. The noninvasive nature of this technique makes it possible to speed up the recovery time after surgery, as well as reduce the number of postoperative complications. Among patients who failed to achieve target pressure after surgery, the use of Brimayza Duo was effective in 62.5% of cases.

Possibilities of Preservative-Free Therapy for Primary Open-Angle Glaucoma

Purpose: to evaluate the efficacy and safety of preservative free travoprost generic in primary open-angle glaucoma patients. Patients and methods. 40 patients with compensated primary open-angle glaucoma (POG) and dry eye (DE) were examined: 1st group (20 patients) with the initial stage of POG (travoprost with a preservative monotherapy), 2nd group with an advanced stage of POG (travoprost with a preservative in combination therapy). In all patients, travoprost with a preservative was replaced with preservative free travoprost (Traviolan, 1 time per day, in the evening). Control: 1 — when included in the study; 2 — 4 weeks after replacing travoprost with a preservative for preservative free travoprost. Efficiency criteria: absence of negative dynamics of intraocular pressure (IOP) and MD and PSD perimetric indices (dB; Optos). Safety criteria: absence of OSDI (scores), tear film brake up time (TBUT; Norn’s test, s), lower tear meniscus height (LTMH, µm; OptoVue) and Bijsterveld’s xerosis index (XI, scores) negative dynamics. Results. At the 2nd control point, all observed did not have a statistically significant dynamics of IOP, MD, PSD. In patients of both groups, at the 2nd control point, there was the OSDI and TBUT statistically significant positive dynamics, and in patients of the 1st group — XI statistically significant positive dynamics. The trend towards to XI decreasing in 2nd group patients and the LTMH dynamics in both groups turned out to be statistically insignificant. Conclusion. Preservative free travoprost has shown efficacy comparable to that of travoprost with preservative in both monotherapy and combination therapy. Significant positive dynamics of OSDI and TBUT in patients of both groups and XI in 1st group patients after switching to preservative free travoprost indicates a good “safety profile” of therapy in terms of its effect on the ocular surface state in DE conditions, which, from our point of view, may contribute to maintaining the “quality of life” and patients compliance.

Topical hypotensive therapy preceding surgical treatment of glaucoma

PURPOSE. To analyze specific clinical and epidemiological parameters of patients with primary open-angle glaucoma (POAG) who were admitted for surgical treatment to the ophthalmological hospital of a multi-specialty in-patient medical center in the period of 2021–2022 years.METHODS. The retrospective elective study analyzed data from 95 patients (95 eyes) with different stages of primary open-angle glaucoma (mean age 73 [67; 80] years old) who were hospitalized for surgical treatment of the disease in 2021–2022. In addition to standard ophthalmological examination, several clinical and epidemiologic characteristics were analyzed in detail, including the prevalence of prescriptions for antiglaucoma hypotensive drugs. Comparison of the obtained results with the data of similar procedures performed in the period from 2005 to 2016 was carried out.RESULTS. The number of main comorbid somatic diseases was on average 3 (2; 4), and comparison of conditions by disease stage revealed no significant differences (p>0.05). Mean duration of the disease (according to anamnesis) was 8 (4; 13) years and was longer in comparison with similar results from 2005–2006 presented in a previous study. The period preceding the first surgical intervention was 5 (2; 10) years and was statistically significantly longer in those with moderate stage of POAG (9 [3; 14] years) compared to those with early stage of POAG (4 [3; 5] years, p<0.05) and advanced stage of POAG (6 [0; 10] years, p<0.04). The average number of drugs at the time of hospitalization for surgical treatment has increased significantly in comparison with the data of the early-mid 2000s and amounted to 4 (3; 4) units (stage I glaucoma — 3 [3; 4]; stage II — 4 [3; 4]; stage III — 4 [3; 4] units), with no statistically significant difference (p1,2=0.64; p1,3=0.21; p2,3=0.42, respectively).CONCLUSION. Unwarranted long-term use of a large number of antiglaucoma drugs ("maximal medication therapy adherence") is a significant problem in modern glaucomatology and can evidently affect future prognosis of the disease.

Correlation analysis of morphofunctional and immunological parameters in patients with advanced stages of primary open-angle glaucoma

PURPOSE. To study the correlations between the immunological data and the indicators of electroretinography (ERG) and optical coherence tomography (OCT) in patients with advanced stages of primary open-angle glaucoma (POAG).METHODS. Previously, we conducted a multimodal study of patients with advanced stages of glaucoma involving ERG, morphometric and immunological studies. In this new study we performed a correlation analysis of the immunological and morphofunctional data of patients with advanced stages of POAG. The study included 35 patients (35 eyes), among them 19 women and 16 men, who were divided into two groups: group 1 — stage II POAG (12 patients, 12 eyes), and group 2 — stage III POAG (23 patients, 23 eyes). The average age of the subjects was 64.2±6.5 years. Intraocular pressure was compensated in all study patients. The Pearson's correlation coefficient was used to calculate the linear relationship between continuous features.RESULTS. In the subgroup with stage II POAG significant correlations of moderate strength (according to the Chaddock scale) were found between the parameters of pattern ERG (PERG) and photopic negative response (PhNR) and the level of VEGF-A in the blood serum (BS), EGF in the tear fluid (TF) and aqueous humor (AH); strong correlations — for the concentrations of EGF and TGF-β2 in the AH. In group 2, moderate correlations between PERG and PhNR parameters and the level of IL-1RA in the TF were found, as well as moderate correlation of TGF-β2 expression in the AH with PnHR amplitude from the baseline. In patients with stage II glaucoma, the levels of MIP-1β/CCL4 in the TF, IL-1RA in the intraocular fluid correlated with the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (GCL), while the EGF in the TF and AH correlated with RNFL thickness. In the group with stage III POAG, correlations of moderate strength were found for the expression level of TNF-α, IL-8/CXCL8 in the TF and RNFL thickness, and strong correlations — for the level of IP-10/CXCL10, HGF/SF, TGF-β2 in AH and the thickness of RNFL and GCL.CONCLUSION. Comparison of ERG, OCT findings and the level of cytokines of various biological effects in the BS, TF and AH confirmed the high informativeness of PERG and PhNR indicators and immunological data as markers of advanced stages of POAG, and allow EGF to be considered as the most promising pathogenetically oriented immunological marker of II and III stages of glaucoma.

Progression detection capabilities of circumpapillary and macular vessel density in advanced glaucomatous eyes

This study investigated the progression detection capabilities of circumpapillary and macular vessel density (cpVD and mVD) in advanced primary open angle glaucoma (POAG) eyes using the rates of change in VD (trend-based analysis) and variability limits derived from healthy eyes. (event-based analysis) This study included 75 POAG eyes [visual field (VF) mean deviation < − 10 decibels, mean follow-up; 2.3 years] and 33 healthy eyes. Of 75 POAG eyes, 17 (22.7 %) and 58 eyes (77.3 %) were classified into the VF progression and stable groups, respectively. The VF progression group showed significantly faster VD loss than the stable group. (cpVD; − 1.76 vs. − 0.84 %/year, mVD; − 1.10 vs. − 0.47 %/year, P < 0.05) However, the rates of change in circumpapillary retinal nerve fiber layer and macular ganglion cell complex thickness were similar between the groups. (cpRNFLT; − 0.67 vs. − 0.53 mum/year, GCCT; − 0.48 vs. − 0.12 mum/year, P > 0.05) Event-based analysis showed stronger agreement between VD and VF progression (cpVD; kappa value (k) = 0.630, mVD; k = 0.667, P < 0.05) than that between structure and VF progression. (cpRNFLT; k = 0.111, GCCT; k = 0.194, P > 0.05). In conclusion, VD loss showed better progression detection capabilities than structural loss in advanced POAG eyes. Detection of cpVD and mVD loss may be useful for detecting progression in the advanced stages of POAG to complement other reference standard strategies.

The electroretinography and optical coherence tomography data matching in patients with advanced stages of glaucoma

AbstractPurposeTo determine the specific changes in the parameters of electroretinography (ERG), reflecting various aspects of retinal ganglion cell (GC) function, and optical coherence tomography (OCT), and their correlations in patients with advanced stages of primary open‐angle glaucoma (POAG).MethodsThe study included 35 people (55 eyes) with stages II and III POAG, divided into two subgroups, and 28 healthy age‐matched individuals (32 eyes). Transient and stationary pattern‐electroretinograms (PERG) and photopic negative response (PhNR) were recorded according to the ISCEV Standards (RETIport/scan, Roland Consult). The thickness of the GC complex (GCC) of the macular region was assessed (Heidelberg Spectralis OCT). The correlation analysis of the GCC indicators and the ERG data was performed. Validation for normal data distribution was performed using the Shapiro‐Wilk test. The Student's t‐test was used to compare normally distributed independent samples. Correlation analysis was performed using Pearson's correlation coefficient.ResultsWe found a reduction in the amplitude of N95 and P50 waves of transient PERG, the stationary PERG, PhNR, and PhNR/b index, and an increase in the peak latency of the N95 and P50 in both patient groups (p &lt; 0.05). A statistically significant thinning of all layers of the GCC was noted in all the studied sectors (p &lt; 0.01). The most essential morphological/functional correlations we determined between the amplitude of stationary PERG and the thickness of the GCC (r &gt; 0.8; p &lt; 0.01). The results showed moderate correlation relationships between parameters of the transient PERG and GCC (r &gt; 0.4; p &lt; 0.01) and between the PhNR amplitude and GCC thickness (r &gt; 0.5; p &lt; 0.01).ConclusionsWe documented specific changes in the morphological and functional parameters of the inner retina in patients with advanced stages of POAG. The detected regularities can be used as clinical markers of the disease and monitor the efficiency of a chosen therapeutic strategy.

YAG-лазерная активация трабекулы в комбинированном лечении первичной открытоугольной глаукомы и осложненной катаракты

Purpose . To study the clinical efficacy of phacoemulsification with YAG-laser activation of trabecula (YAG-LAT) in eyes with primary openangle glaucoma (POAG) and coexisting complicated cataract. Material and methods . The study included 70 patients (70 eyes) with initial and advanced stages of POAG and coexisting cataract. There were 42 women (60%) and 28 men (40%), the average age was 68.8±8.2 years. The follow-up period is 2 years after the treatment. The patients were divided into two groups: combined group – 36 patients (36 eyes) who underwent YAG-LAT and phacoemulsification and the control group – 34 patients (34 eyes) who underwent phacoemulsification alone. The baseline IOP by Maklakov in the combined and control groups was 24.1±2.52 and 23.0±2.41 mm Hg respectively. The mean medication use was 1.53±0.65 in the combined group and 1.44±0.50 in the control group. Results . There were no intraoperative complications. In the early postoperative period, reactive increase in IOP was noted in 8.3 and 32.4% of cases in the combined and control groups, respectively. By the end of the follow-up period, the mean IOP decreased by 21.1% after combined treatment (p<0.001) and in the control group, no statistically significant differences were revealed. The mean medication use decreased from 1.53±0.65 to 0.64±0.56 after combined treatment (p<0.05), and increased from 1.44±0.50 to 1.92±0.28 after phacoemulsification alone (p<0.05). Conclusion . In long-term follow-up after combined treatment (YAGLAT with phacoemulsification) normalization of IOP was achieved in 96.4% of cases, the mean medication use decreased significantly, stabilization of the glaucoma process was noted in 96.4% of cases. Increased visual acuity after treatment was observed in all patients in both groups. The developed method of treatment is safe, has a minimal risk of complications and can be used to treat patients with the initial stages of POAG and coexisting cataract.

Особенности содержания трансформирующих факторов роста – бета 1,2,3 (TGF-β1, TGF-β2, TGF-β3) во внутриглазной жидкости при первичной открытоугольной глаукоме

Purpose. To study transforming growth factors – beta 1,2,3 (TGF-β1, TGF-β2, TGF-β3) in intraocular aqueous humor (AH) of patients with the advanced stage of primary open angle glaucoma (POAG). Material and methods. The study included an examination of 56 patients with advanced stage of POAG which comprised the main group. The diagnosis of POAG was confirmed based on ophthalmological examination. The control group consisted of 30 patients with uncomplicated cataract. TGF-β isoforms concentrations were detected by flow fluorimetry using Bio-Plex Pro™ TGF-β 3-plex Assay and double-beam laser analyzer Bio-Plex 200, Bio-Rad, USA. Three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were simultaneously detected in AH. Results. The study revealed a significant increase of TGF-β isoforms concentrations in AH of the advanced POAG compared to AH of the group with uncomplicated cataract: TGF-β1 (3.1 times higher), TGF-β2 (1.4 times) and TGF-β3 (6.9 times). The following direct significant correlations were found: between TGF-β1 and TGF-β2 (r=0.41, p<0.03), between TGF-β1 and TGF-β3 (r=0.83, p<0.004), and between TGF-β2 and TGF-β3 (r=0.35, p<0.04). Conclusion. We determined a simultaneous increase of concentrations of the studied representatives of super-family transforming growth factors, which have an anti-inflammatory activity, potential to stimulate proliferation, cellular growth, synthesis of proteins of extracellular matrix, etc. These results prove their importance in the POAG pathogenesis.

Structure and Function Relationship of Activated Retinal Glia in Primary Open-Angle Glaucoma Patients.

Purpose To evaluate clinically activated retinal astrocytes and Müller cells (ARAM) regarding retinal sensitivity and retinal nerve fiber layer (RNFL) thickness in primary open-angle glaucoma (POAG). Methods Central visual field (VF; i.e., retinal sensitivity) was measured with a custom-made macular pattern by microperimetry and correlated with the presence (ARAM+) or absence (ARAM−) of ARAM on red-free fundus photography and with the corresponding RNFL by optical coherence tomography (OCT). Results In the eyes of POAG patients, ARAM+ had overall a significantly lower retinal sensitivity (ARAM+: 7.34 dB, ARAM−: 11.9 dB; p < 0.001) and lower RNFL thickness in the inferior peripapillary quadrants compared to ARAM− (RNFL superior: ARAM+ 74.2 μm, ARAM− 77.5 μm; RNFL temporal: ARAM+ 46.8 μm, ARAM− 53.0 μm, p < 0.001; and RNFL inferior: ARAM+ 63.2 μm, ARAM− 73.1 μm, p < 0.001). Within the same eye, ARAM+ showed a lower retinal sensitivity compared to ARAM− ([ARAM− (11.13 dB)] − [ARAM+ (9.56 dB) = 1.57 dB; p = 0.25). The proportion of ARAM+ per eye correlated strongly with reduced retinal light sensitivity (p = 0.02), corresponding lower peripapillary RNFL thickness (p = 0.02), and lower RNFL temporal quadrant thickness (p < 0.01), but not with greater age (p = 0.45). Conclusion ARAM was more frequently identified in the eyes with a lower retinal sensitivity and peripapillary RNFL thickness and may be a clinical sign in the macula for an advanced stage of POAG.

Introducing and measuring cornea and sclera deformability parameters on the basis of Schiøtz tonometry: mathematical modeling and clinical evaluation in Primary Open Angle Glaucoma (POAG)

PurposeTo obtain additional information on the biomechanical status of the eyeball on the basis of static loading by the Schiøtz tonometer, to be applied to POAG.MethodsEarlier, we proposed a mechanically correct theory of Schiøtz tonometry, which represents the eyeball as a shell characterized by two elastic constants separately responsible for the cornea and the sclera properties, and used the theory here. We examined 41 patients (43 eyes) aged 55–72 (mean age 64 ± 4.0 years) with non‐operated POAG, including 20 eyes with early and 23 eyes with advanced stage of POAG. 15 patients with no eye pathology of the same age group served as control. The examination included differential Schiøtz tonometry using a GlauTest 60 tonograph.ResultsApplicability limits are estimated for the standard relations used in processing the clinical data. Based on differential tonometry, we introduced a coefficient γ, equal to the ratio of the IOP difference to the plunger weight difference, and looked at how γ depends on the cornea and sclera stiffness and the true IOP. The γ coefficient, which mainly characterizes the scleral rigidity, was determined at 1.65 ± 0.25 mm Hg/g for the early stage of POAG and 1.88 ± 0.13 mm Hg/g for the advanced POAG stage, with a control group average of 1.47 ± 0.10 mm Hg/g (p &lt; 0.05). On average, γ was 27% greater for the POAG patients, whereas the mean Friedenwald's rigidity coefficient only differed from the norm by 7%.ConclusionsChanges in the mechanical parameter proposed testify to changes in the elastic characteristics of the eyeball in POAG. The coefficient γ reflects individual abnormalities of the biomechanical status of the sclera for the glaucomatous eye more adequately than Friedenwald's rigidity coefficient. Practical recommendations are proposed.The study was supported by RFBR (project No. 14‐01‐00475).

Photopic negative response of full-field electroretinography in patients with different stages of glaucomatous optic neuropathy

PurposeTo evaluate photopic negative response (PhNR) discrimination ability between healthy and glaucomatous patients. MethodsNinety eyes of 50 patients with primary open angle glaucoma (POAG) and 45 eyes of 23 healthy age- and sex-matched controls were investigated. Based on European Glaucoma Society criteria, POAG patients were divided into three groups: early, moderate and advanced glaucoma. Following measurements were analysed: mean defect (MD) from Humphrey Visual Field Analyzer, SITA standard 24-2 white on white perimetry; nerve fibre index (NFI) obtained from scanning laser polarimetry; and GDx and PhNR amplitude and PhNR/b-wave ratio. PhNR was elicited by red stimuli with flash strength of 1.6 cd s/m2 on blue background of 25 cd/m2. Correlations between retinal ganglion cells function (PhNR), retinal sensitivity (MD) and structure (NFI) were calculated. Sensitivity and specificity of PhNR parameters were calculated with standard formulas. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values. The area under the curve (AUC) was used to compare the ROC curves results between PhNR amplitude and ratio.ResultsPhNR amplitude and ratio were significantly reduced in early, moderate and advanced glaucoma groups compared to controls. The sensitivity and specificity to detect glaucoma in early POAG were equal to 53.3 and 90.0 % for PhNR amplitude and 60.0 and 70.0 % for PhNR ratio; in moderate POAG 63.3 and 80.0 % for PhNR amplitude and 60.0 and 86.7 % for PhNR ratio; and in advanced POAG 76.6 and 80.0 % for PhNR amplitude, 90.0 and 73.3 % for PhNR ratio. There were no significant differences between AUC for PhNR amplitude (0.76–0.86) and PhNR ratio (0.78–0.86), p > 0.05. PhNR amplitudes and ratios correlated significantly with MD measured by SAP and NFI obtained from GDx (p < 0.05). PhNR amplitude significantly decreases with advancement of visual field defects in glaucoma patients.ConclusionsPhNR reveals dysfunction of RGCs in early, moderate and advanced stage of POAG. PhNR has good discrimination ability in detecting glaucomatous patients. PhNR might be a useful test in glaucoma diagnosis.

Functional and hemodynamic parameters in glaucoma patients after trabeculectomy

Abstract Purpose To study a correlation of hemodynamic and electroretinography (ERG) parameters in patients with primary open angle glaucoma (POAG) before and after trabeculectomy. Methods 29 patients (32 eyes) with early, advanced and late stages of POAG were tested prior to surgery and at 2 months after trabeculectomy. Standard ERG methods and chromatic macular ERG were used. Ocular hemodynamics were evaluated by colour Doppler sonography. Peak systolic velocities (PSV), end‐diastolic velocities (EDV), and resistive indices (RI) of the ophthalmic artery, central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were obtained. Results After surgery reduction of IOP (62.7%, p≤0.001) revealed a significant increase of amplitude values of OPs and macular ERG (p≤0.05). In early and late stages of POAG there were no significant differences in ocular blood flow parameters before and after trabeculectomy. In advanced stage the PSV and EDV in CRA were increased (p≤0.05). We found a correlation between macular ERG to red stimuli, OPs and blood flow parameters in CRA and SPCA before trabeculectomy. After surgery statistics revealed a correlation only between OPs and PSV in CRA. Conclusion The functional changes of macular area and inner retina are more common in patients with simultaneous decrease of PSV and EDV in CRA and SPCA. Retinal bioelectric activity in early and advanced stages of POAG is IOP‐dependent, and can be partially restored after IOP reduction. In contrast to ERG, the retinal blood parameters are relatively constant before and after short period of trabeculectomy.

Primary Open-Angle Glaucoma: Diagnostic Approaches and Management

Glaucoma represents the second most common cause of blindness in the United States affecting approximately 2 million Americans, with many others unaware of being afflicted. Primary open-angle glaucoma (POAG), which is the most common of all types of glaucoma, leads to progressive optic nerve damage. If left untreated, POAG can lead to irreversible blindness. Since POAG is a relatively asymptomatic disease, prevention of long-term complications must be accomplished with regular screening for early detection and appropriate treatment. Primary care physicians play a critical role in screening at-risk populations and, therefore, reducing the risk of visual loss that characterizes advanced stages of POAG.

Functional activity of the retina before and after IOP normalization in glaucoma

Abstract Purpose To study dynamics of bioelectrical activity of the retina before and after normalization of intraocular pressure (IOP) in primary open angle glaucoma (POAG). Methods 20 normal subjects and 68 patients with different stages of glaucoma (early–I, advanced – II, late – III) and high level of IOP were included in our study. IOP ranged from 27 to 36 mmHg. All patients underwent complete eye examination, HRT II imaging, ERG including full‐field, flicker, pattern ERG (PERG), oscillatory potentials (OP), long‐duration flash ERG, chromatic macular ERG to red, green and blue stimuli (MBN, Russia). Results Different decrease of ERG amplitudes were detected depending on the stage of POAG. Subnormal flicker, as well as subnormal macular ERG to red and green stimuli, diminished or unrecordable off‐response were observed in all stages of POAG with increased IOP. A pathological configuration and decreased amplitudes of OPs, prolonged N95‐component of PERG and subnormal full‐field ERG was revealed in advanced and late stages of glaucoma. After reduction of IOP significant increase of amplitude values and shortening of implicit time (IT) were observed in early and advanced stages of POAG (p≤0,05), whereas those in late stage of POAG showed slight positive dynamics. Conclusion ERG symptoms in POAG have high value for assessment the functional state of the retina and optic nerve, determination of degree of IOP normalization and must be used in treatment control.