Glaucoma Diagnostic Performance of Macular Ganglion Cell Complex Thickness Using Regular and Long Axial Length Normative Databases

The risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals, due to considerable morphologic variability in high myopic fundus. This study aims to compare the diagnostic ability of the regular and long axial length databases in the RS-3000 Advance SD-OCT (Nidek) device to correctly diagnose glaucoma with high myopia. Patients with high myopia (axial length ≥ 26.0 mm) in Chang Gung Memorial Hospital, Taiwan between 2015 and 2020 were included. Glaucoma was diagnosed based on glaucomatous discs, visual field defects and corresponding retinal nerve fiber layer defects. The sensitivity, specificity, diagnostic accuracy and likelihood ratios of diagnosing glaucoma via mGCC thickness in both superior/inferior and GChart mapping using the regular and long axial length normative databases. The specificity and diagnostic accuracy of mGCC thickness for distinguishing glaucomatous eyes from nonglaucomatous eyes among highly myopic eyes were significantly improved using the long axial length database (p=0.046). There were also significant proportion changes in S/I mapping as well as GChart mapping (37.3% and 48.0%, respectively; p<0.01) from abnormal to normal in the myopic normal eye group when using the long axial length normative database. The study revealed that clinicians could utilize a long axial length database to effectively decrease the number of false-positive diagnoses or to correctly identify highly myopic normal eyes misdiagnosed as glaucomatous eyes.

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma

Background/aimsTo investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD).MethodsPOAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models.ResultsThirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: −0.50 (95% CI −0.83 to –0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively).ConclusionIn POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

Preservative free travoprost and timolol fixed combination in the initial treatment of primary glaucoma: an assessment of hypotensive efficiency and safety

Purpose. To evaluate the efficacy and safety of Travapress Duo with respect to hypotensive results, changes in functional parameters, and adverse reactions. Material and methods. 30 patients aged 65–75 (averagely 71.3 ± 3.2 years) with a newly diagnosed primary open-angle glaucoma (POAG) received Travapress Duo in the evening, once a day. Goldman tonometry was performed during the screening, then 1 week, 1 month and 3 months from the treatment start. Static perimetry and optical coherence tomography (OCT) were performed before treatment and at the end of the 3rd month since the treatment start. Adverse events were recorded at each stage of the study.Results. As a result of a 3 month long therapy with Travapress Duo, a significant decrease in IOP was noted starting from the 1st week of instillations (by 34 %), after 1 month, by 35 % and after 3 months of observation by 36 %. By the end of the 3rd month of treatment, we noted an insignificant increase in visual acuity, a positive dynamic of the standard deviation and the standard deviation pattern, as well as OCT indicators, such as average thickness of the layer of retinal nerve fibers and the layer of retinal ganglion cells in the macula, stabilization of the thickness of the retinal ganglion cell complex layer and the size of the inner plexiform layer. One patient complained of discomfort and hyperemia by the end of the 1st week of drug instillation. No systemic side effects were noted during the follow-up, and in no case drug withdrawal was require. Conclusion. The preservative-free Travapress Duo drug displayed a high hypotensive efficacy, reducing the IOP to 36% of the initial value. The hypotensive effect was accompanied by indirect neuroprotection, which manifested itself in the positive changes observable in the results of functional studies with varying degrees of reliability. Travapress Duo is characterized by a low level of local side effects and can be recommended for both for the initial and long-term therapy of primary glaucoma of developed and advanced stages.

Vascular and vegetative factors of glaucoma attack

Purpose. To study the involvement of vascular and vegetative factors in the pathogenesis of glaucoma attack. Material and methods. 12 patients (24 eyes) aged 49 to 82 — 5 men and 7 women, including 3 patients with acute glaucoma and 9 patients with subacute glaucoma were subjected to an ophthalmological examination that included visometry, tonometry, automated static perimetry, OCT and OCT angiography. They were also tested for heart rate variability (HRV) using a Polar heart rate monitor, and for plasminogen content and products of fibrin/fibrinogen degradation in the tear. For comparison, the contralateral eyes of these patients were examined. Results. In the eyes with an acute glaucoma attack, the vascular network was noticeably weakened, especially in the area of the deep peripapillary vascular plexus at the lamina cribrosa level, and focal capillary loss was observed. The peripapillary density of the deep vascular plexus in the eyes with an acute attack was 33.0 ± 5.6 % (М ± m), which was significantly (p < 0.01) lower as compared to 50.0 ± 4.7 % in the unaffected eyes. This indicator correlated with the thickness of the ganglion cell complex (GCC) (p < 0.01). In unaffected eyes, no correlations were found between these glaucoma-related parameters. A significant amount of fibrin/fibrinogen degradation products was found in the tear of glaucoma patients, which may point to a violation of blood circulation in the optic nerve vessels. It has been established that glaucoma attack occurs with increased activity of sympathetic regulation of blood flow. Conclusion. When monitoring this contingent of patients, it is essential to determine the sympathetic-parasympathetic status of the patient. Taking into account the vascular component of the condition, it is expedient to introduce the necessary additions into its treatment plans

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.

Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas

Background and Objective: Retinal ischemia-reperfusion (IR) leads to massive loss of retinal ganglion cells (RGC) and characterizes several blind-causing ophthalmic diseases. However, the mechanism related to retinal IR is controversial, and a drug that could prevent the RGC loss caused by IR is still lacking. This study aimed to investigate the role of endogenous retinal peroxisome proliferator-activated receptor (PPAR)α and the therapeutic effect of its agonist, fenofibric acid (FA), in IR-related retinopathy.Materials and Methods: Fenofibric acid treatment was applied to the Sprague–Dawley rats with IR and retinal cell line 28 cells with oxygen-glucose deprivation (OGD) (an in vitro model of IR). Western blotting, real-time PCR, and immunofluorescence were used to examine the expression levels of PPARα, glial fibrillary acidic protein (GFAP), and cyclooxygenase-2 (COX2). Hematoxylin and eosin (HE) staining, propidium iodide (PI) staining, retrograde tracing, and flash visual-evoked potential (FVEP) were applied to assess RGC injury and visual function.Results: Retinal IR down-regulated PPARα expression in vitro and in vivo. Peroxisome proliferator-activated receptor α activation by FA promoted survival of RGCs, mitigated thinning of the ganglion cell complex, and decreased the latency of positive waves of FVEPs after IR injury. Further, FA treatment enhanced the expression of endogenous PPARα and suppressed the expression of GFAP and COX2 significantly.Conclusion: Peroxisome proliferator-activated receptor α activation by FA is protective against RGC loss in retinal IR condition, which may occur by restoring PPARα expression, inhibiting activation of glial cells, and suppressing retinal inflammation. All these findings indicate the translational potential of FA in treating IR-related retinopathy.

Long-term reproducibility of optical coherence tomography angiography in healthy and stable glaucomatous eyes

Background/aimsTo assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes.MethodsEighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1–1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates.ResultsICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test–retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities.ConclusionsOCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change.Trial registration numberNCT00221897.

High-Resolution Image Analysis Reveals a Decrease in Lens Thickness and Cone Density in a Cohort of Young Myopic Patients

Purpose: To study the association between axial length (AL) and the thickness of the lens, retina, choroid, and cone density with swept-source optical coherence tomography (SS-OCT) and an adaptive optics (AO) fundus camera.Design: A prospective cross-sectional study.Methods: This study included 136 eyes in 68 subjects. SS-OCT was used to quantify the thickness of the lens, ganglion cell complex (GCC) layer, inner nuclear layer (INL), outer retinal layer (ORL), and choroid layer. Adaptive optics was used to quantify spatial features of the cone photoreceptors, including density, spacing, regularity, and dispersion. The associations among the AL and the thickness of lens, retina, choroid, and cone features were evaluated with linear regression.Results: With the severity of myopia, the increased AL was associated with thinning of the lens (P &lt; 0.001, 95% CI: −100.42 to −49.76). The thickness of the ORL and choroid decreased significantly (all P &lt; 0.001), whereas the thickness of the GCC and INL decreased only in the outer ring (both P &lt; 0.01). There was a significant correlation between the cone density/spacing and AL (both P &lt; 0.001). Although cone density was reduced from 25,160/mm2 to 19,134/mm2 in the inner region and from 17,458/mm2 to 13,896/mm2 in the outer region, the best-corrected visual acuity (BCVA) was 20/20 or greater.Conclusions: We found that the lens thickness (LT), ORL, and cone density decreased in myopia. While decreasing cone density and ORL thickness should be related to axial elongation, decreasing of LT might imply intrinsic physical accommodation. These results provide further morphological changes of myopia.

The Diagnostic Value of Pulsar Perimetry, Optical Coherence Tomography, and Optical Coherence Tomography Angiography in Pre-Perimetric and Perimetric Glaucoma

The purpose of this article is to investigate the diagnostic value of Pulsar perimetry (PP), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) in pre-perimetric glaucoma (PPG) and perimetric glaucoma (PG). This retrospective cross-sectional study included 202 eyes (145 eyes in the control group, 40 eyes in the PPG group, and 17 eyes in the PG group) from 105 subjects. The results were analyzed by paired t-tests and Wilcoxon signed-rank test. The area under the curve (AUC), sensitivity, and specificity were used to evaluate the diagnostic accuracy. Pearson correlation was used to investigate the relationships of each parameter. The most sensitive parameters for differentiating the control group from the PPG group by using Pulsar, OCT, and OCTA were square loss variance of PP (AUC = 0.673, p < 0.001), superior ganglion cell complex thickness (AUC = 0.860, p < 0.001), and superior-hemi retina thickness (AUC = 0.817, p < 0.001). In the PG group, the most sensitive parameters were mean defect of PP (AUC = 0.885, p < 0.001), whole image of ganglion cell complex thickness (AUC = 0.847, p < 0.001), and perifoveal retina thickness (AUC = 0.833, p < 0.001). The mean defect of PP was significantly correlated with vascular parameters (radial peripapillary capillary (RPC), p = 0.008; vessel density of macular superficial vascular complex (VDms), p = 0.001; vessel density of macular deep vascular complex (VDmd), p = 0.002). In conclusion, structural measurements using OCT were more sensitive than vascular measurements of OCTA and functional measurements of PP for PPG, while PP was more sensitive than the structural and vascular measurements for PG. The mean defect of PP was also shown to be highly correlated with the reduction of vessel density.