Circular functional analysis of OCT data for precise identification of structural phenotypes in the eye

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and present challenges to clinical decision-making. We generated a dataset of Optical Coherence Tomography (OCT) based high-resolution circular measurements on NRR phenotypes, along with other clinical covariates, of 3973 healthy eyes as part of an established clinical cohort of Asian Indian participants. We introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, followed by meta-clustering to characterize the clusters using clinical covariates, and presented a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40–49 years with predictive potential for glaucoma. Our dataset also addresses the disparity of representation of this particular population in normative OCT databases.

Disc damage likelihood scale recognition for Glaucoma detection

Glaucoma is a visual disorder, which is one of the significant driving reason for visual impairment. Glaucoma leads to frustrate the visual information transmission to the brain. Dissimilar to other eye illness such as myopia and cataracts. The impact of glaucoma can’t be cured; The Disc Damage Likelihood Scale (DDLS) can be used to assess the Glaucoma. The proposed methodology suggested simple method to extract Neuroretinal rim (NRM) region then dividing the region into four sectors after that calculate the width for each sector and select the minimum value to use it in DDLS factor. The feature was fed to the SVM classification algorithm, the DDLS successfully classified Glaucoma disease with 70% percentage; moreover, when the dimensions of both Optic Disc(OD) and Optic Cup(OC) were used as additional features the accuracy rate raised to 91%.

Comparitive study between normal tension glaucoma and primary open-angle glaucoma

The study is conducted to determine the functional and structural differences between NTG and POAG, to assess the rate of conversion of NTG into POAG and its early intervention. It is a hospital based prospective, cross-sectional study of 56 NTG and 56 POAG patients. History was taken and comprehensive ophthalmic examination with glaucoma work up was done.Majority of the patients belonged to the age group between 51 and 60 years i.e. 48.2% in NTG and 62.5% in POAG. Majority of the NTG patients i.e. 33 (58.9%) were females while 41(73.2%) were males in POAG. 40% of NTG patients had systemic association like bronchial asthma, diabetes, hypertension, ischemic heart disease and migraine. There was no significant difference in CDR between two groups. Inferior & temporal neuroretinal rim thinning was more common in NTG. While bipolar thinning & superior rim thinning was more common in POAG. There is significantly more thinning of RNFL in POAG than NTG. The mean deviation (MD) & pattern standard deviation (PSD) in visual fields between NTG & POAG showed no significant difference. Whereas the field loss was near centre of fixation in NTG group compared to POAG which was diffuse. These differences between NTG and POAG suggest that the pathogenesis of NTG includes IOP and IOP independent risk factors, while IOP is the main risk factor in POAG. The parameters assessed determine the risk and progression of NTG to POAG.

Factors Associated with Increased Neuroretinal Rim Thickness Measured Based on Bruch’s Membrane Opening-Minimum Rim Width after Trabeculectomy

Purpose: To investigate the factors associated with an increase in the neuroretinal rim (NRR) thickness measured based on Bruch’s membrane opening-minimum rim width (BMO-MRW) after trabeculectomy in patients with primary open-angle glaucoma (POAG). Methods: We analyzed the BMO-MRW using spectral-domain optical coherence tomography (SD-OCT) of patients with POAG who underwent a trabeculectomy for uncontrolled intraocular pressure (IOP) despite maximal IOP reduction treatment. The BMO-MRW was measured before and after trabeculectomy in patients with POAG. Demographic and systemic factors, ocular factors, pre- and post-operative IOP, and visual field parameters were collected, together with SD-OCT measurements. A regression analysis was performed to investigate the factors that affected the change in the BMO-MRW after the trabeculectomy. Results: Forty-four eyes of 44 patients were included in the analysis. The IOP significantly decreased from a preoperative 27.0 mmHg to a postoperative 10.5 mmHg. The mean interval between the trabeculectomy and the date of post-operative SD-OCT measurement was 3.3 months. The global and sectoral BMO-MRW significantly increased after trabeculectomy, whereas the peripapillary retinal nerve fiber layer thickness did not show a difference between before and after the trabeculectomy. Younger age and a greater reduction in the IOP after the trabeculectomy were significantly associated with the increase in the BMO-MRW after trabeculectomy. Conclusions: The NRR thickness measured based on the BMO-MRW increased with decreasing IOP after trabeculectomy, and the increase in the BMO-MRW was associated with the young age of the patients and greater reduction in the IOP after trabeculectomy. Biomechanically, these suggest that the NRR comprises cells and substances that sensitively respond to changes in the IOP and age.

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 μm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5–6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.

Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients

Purpose Agonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG. Material and methods Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb. Results (I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028). Conclusion FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.

Bruch’s membrane opening-minimum rim width: An alternative OCT biomarker study for multiple sclerosis

Purpose: Bruch’s membrane opening-minimum rim width (BMO-MRW) and RNFL measured using anatomic positioning system (APS-RNFL) are novel OCT methods and remained unexplored in MS patients. To investigate the novel parameters of spectral-domain OCT as an alternative biomarker in patients with multiple sclerosis (MS). Methods: Retrospective cohort study; participants consisted of relapsing-remitting MS (RRMS) patients and healthy controls (HC). Eyes were classified according to the presence of MS and previous optic neuritis (ON). Measurements of standard peripapillary RNFL (S-RNFL), BMO-MRW, and APS-RNFL were performed. Result: A total of 244 eyes of 122 participants (MS-patients: 63, HC: 59) were included in the study. Fifty-one eyes had a history of previous ON. In almost all measured parameters, neuroretinal rim thicknesses were observed the thinnest in eyes with ON history between all subgroups. S-RNFL and APS-RNFL techniques showed the difference in neuroretinal rim thickness in all three subjects (ON+, ON−, and HC). However, BMO-MRW, on the other hand, could not distinguish between ON(−) patients and HC. The relationship between OCT parameters and EDSS were observed only in eyes with an ON history in all three techniques. A meaningful model with 78% accuracy was obtained by using only the OCT parameters as risk factors. In the ROC analysis, no parameters were found to have acceptable high sensitivity and specificity. BMO-MRW was statistically weaker in every aspect than other RNFL techniques. Conclusion: The novel APS-RNFL technique appears to be a bit more reliable alternative to S-RNFL technique to support therapeutic decision-making in MS. BMO-MRW has not been found as a successful alternative to S-RNFL.