Progressive Retinal Nerve Fiber Layer Research Articles

Goniosynechialysis for Chronic Angle-closure Glaucoma after Extracapsular Cataract Extraction: A Case Report

Purpose: We present a case of goniosynechiolysis in the treatment of chronic angle-closure glaucoma with persistent peripheral anterior synechia (PAS) after extracapsular cataract extraction (ECCE) for phacomorphic glaucoma that remained uncontrolled using topical glaucoma medications.Case summary: A 59-year-old woman presented with right eye pain and visual loss that started 3 days ago. Examination revealed an intraocular pressure (IOP) of 46 mmHg, a narrow central anterior chamber, and peripheral iridocorneal touch, indicative of phacomorphic glaucoma. Although ECCE was performed, PAS was not adequately resolved. Initially, visual acuity, IOP, and visual field were controlled with a single topical glaucoma medication. However, progressive retinal nerve fiber layer thinning and uncontrolled IOP, despite maximal medical therapy. Therefore, goniosynechiolysis was performed at 24 months after ECCE. The procedure reduced IOP from 25 mmHg to 13 mmHg without complications, such as hyphema, cyclodialysis, and fibrin formation.Conclusions: Goniosynechiolysis can be a safe and effective intervention for chronic angle-closure glaucoma with persistent PAS and elevated IOP.

Diagnosing glaucoma progression with optical coherence tomography.

Optical coherence tomography (OCT) is a widely used tool to diagnose and monitor glaucoma by objectively measuring the ganglion cell layer and the retinal nerve fiber layer (RNFL) thickness. The presence of RNFL thinning raises suspicion for glaucoma progression. Therefore, this review aims to discuss current approaches to using OCT for detecting glaucomatous change, limitations, and recent advancements. Previously established approaches to determining glaucomatous progression on OCT include quantitative and qualitative methods. The most common quantitative methods include event-based and trend-based analysis. Decreasing RNFL thickness or loss of the ganglion cell layer are indicative of glaucomatous changes. However, interpretation of OCT scans is strongly impacted by artifacts, which can be because of epiretinal membrane or posterior vitreous detachment. Race and aging also may impact interpretation of RNFL progression. More recent research focuses on loss of the RNFL because of the effects of systemic conditions. Given the limitations in the current approaches, recent advancements indicate a promising role for artificial intelligence in determining true glaucomatous progression. This review highlights current approaches to identifying glaucoma progression on OCT, limitations to these approaches, and the potential role for artificial intelligence.

Small extracellular vesicles derived from microRNA-22-3p-overexpressing mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study

PurposeTo observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DesignRetrospective, longitudinal, observational study. ParticipantsNinety-five patients with unilateral NTG and 61 healthy controls MethodsThis study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable RNFL thickness (RNFLT) measurements were performed using optical coherence tomography. Factors associated with the rate of thinning of the unaffected eyes of unilateral NTG patients were identified using regression analysis. Main Outcome MeasuresThe rate of progressive RNFL thinning and the associated factors. ResultsRNFLT decreased significantly in both the unaffected eyes of unilateral NTG patients and the healthy eyes (both P<0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral NTG patients than in the healthy eyes (P<0.001), specifically in the temporal-inferior sector (P=0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral NTG patients were thicker baseline RNFL of the unaffected eyes (P=0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P=0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P=0.007). ConclusionsThe unaffected eyes of unilateral NTG patients showed faster RNFL thinning than healthy control eyes, more obviously in the temporal-inferior sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral NTG patients, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma.

Comparison of Patterns of Structural Progression in Primary Open Angle Glaucoma and Pseudoexfoliation Glaucoma.

Primary open angle glaucoma and pseudoexfoliation glaucoma showed different progression patterns of the retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning in OCT-guided progression analysis. To compare the patterns of progression of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning by guided progression analysis (GPA) of optical coherence tomography (OCT) in primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). The progression of RNFL and GCIPL thinning was assessed by the GPA of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). By overlaying the acquired images of the RNFL and GCIPL thickness-change maps, the topographic patterns of progressive RNFL and GCIPL thinning were evaluated. The rates of progression of RNFL and GCIPL thinning were analyzed and compared between patients with POAG and those with PXG. Of the 248 eyes of 248 patients with POAG (175 eyes of 175 patients) or PXG (73 eyes of 73 patients) enrolled, 156 POAG eyes and 48 PXG eyes were included. Progressive RNFL thinning was significantly more common in PXG than in POAG ( P =0.005). According to the RNFL progression-frequency maps, progression appeared mainly in the superotemporal and inferotemporal areas in POAG, whereas it had invaded more into the temporal area in PXG. According to the GCIPL maps, progression was most common in the inferotemporal area in both POAG and PXG. The average progression rate of GCIPL thinning was faster in PXG than in POAG ( P =0.013), and when analyzed in 2 halves (superior/inferior), the progression rate of the inferior half was faster in PXG than in POAG ( P =0.011). OCT GPA showed progression patterns of RNFL and GCIPL thinning in POAG and PXG. Understanding the specific patterns of progressive RNFL and GCIPL thinning according to glaucoma type may prove helpful to glaucoma-patient treatment and monitoring.

Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures

To assess longitudinal relationships among visual function and anatomical measures of gene therapy in G11778A Leber hereditary optic neuropathy (LHON). Phase 1 clinical trial. This was a single-institution study of patients with G11778A LHON. Patients with chronic bilateral visual loss >12 months (group 1, n=11), acute bilateral visual loss <12 months (group 2, n=9), or unilateral visual loss (group 3, n=8) were administered unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. Oucome measures were best-corrected visual acuity (BCVA), visual field mean deviation (VF MD), steady-state pattern electroretinogram (SS-PERG), optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and ganglion cell+inner plexiform layer (GCIPL) thickness, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Mean follow-up was 33.6 months (range=18-36 months). Baseline SS-PERG amplitude was much reduced in both eyes of all groups including asymptomatic eyes of group 3, and showed no appreciable changes irrespective of disease stage and treatment. Significant and progressive GCIPL and RNFL thinning occurred in all eyes; BCVA and VF MD fluctuated in treated and fellow eyes, with some eyes having modest improvement that may be related to natural history or to gene therapy. Mean NEI-VFQ-25 scores declined in group 3 subjects (P=.023), CONCLUSION: Asymptomatic eyes in LHON patients with unilateral visual loss may be beyond the window of effective neuroprotection given reduced GCIPL and SS-PERG. Randomization of patients to an untreated control group would help to assess treatment effect by accounting for variable natural history. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Optic Nerve Head Morphology is Associated with the Initial Location of Structural Progression in Early Open-Angle Glaucoma.

To investigate the effects of clinical variables on the temporal relationship between macular ganglion cell-inner plexiform layer (mGCIPL) loss and peripapillary retinal nerve fiber layer (pRNFL) loss in glaucoma. Glaucoma eyes with a small cup-to-disc ratio tend to show retinal nerve fiber layer progression earlier than ganglion cell-inner plexiform layer progression. This retrospective observational study used medical records of patients diagnosed with open-angle glaucoma. Structural change was determined using guided progression analysis software of Cirrus optical coherence tomography. Based on the time of detection of pRNFL and mGCIPL changes, eyes showing progressive layer loss were categorized into the pRNFL-first and mGCIPL-first groups. The association between sites of layer thinning and clinical variables such as major retinal arterial angles and several optic disc measurements including disc area, average cup-to-disc ratio (CDR), and vertical CDR were analyzed. A total of 282 eyes were included in the study, of which 104 showed structural progression either in the mGCIPL or pRNFL. Out of these, 49 eyes showed first progression in pRNFL, while 37 eyes showed first progression in mGCIPL. The minimum mGCIPL thickness, pRNFL thickness, average CDR, vertical CDR, and location of progression were significantly different between the two groups (P=0.041, P=0.034, P=0.015, P<0.001, and P<0.001, respectively). In multivariate analysis, average CDR and vertical CDR were significantly associated with the progression site (P=0.033 and P=0.006, respectively). The structural changes in the inferoinferior area and the superior vulnerability zone were significantly associated with RNFL-first progression (P<0.001 for both). The location of layer loss and CDR are related to the layer where loss is first detected (either pRNFL or mGCIPL) in open-angle glaucoma.

Discrepancy between peripapillary retinal and choroidal microvasculature and the rate of localized retinal nerve fiber layer thinning in glaucoma

This observational case series study is conducted to compare the extent of microvasculature impairment in the peripapillary retina and choroid in eyes with primary open-angle glaucoma (POAG), and to investigate the association of the discrepancy between the microvasculature impairments of each layer with the rate of progressive retinal nerve fiber layer (RNFL) thinning. A total of 88 POAG eyes with a localized RNFL defect were enrolled, including 67 eyes with and 21 eyes without choroidal microvasculature dropout (CMvD). Circumferential widths of retinal microvascular impairment (RMvI) and CMvD were measured, and eyes were classified based on the relative width of CMvD to RMvI (CMvD/RMvI ratio). The rate of RNFL thinning was determined by linear regression based on ≥ 5 serial OCT examinations. Thinner global RNFL and worse visual field mean deviation at baseline were associated with a larger circumferential width of the RMvI, whereas the presence of cold extremities, lower mean arterial pressure and thinner juxtapapillary choroid were associated with a larger circumferential width of the CMvD. The rate of global RNFL thinning was faster in eyes with larger relative CMvD width than in eyes with equal CMvD and RMvI widths and in eyes without CMvD (P = 0.001). Lower mean arterial pressure (P = 0.041), larger CMvD width (P = 0.046), larger CMvD/RMvI ratio (P = 0.041), and detection of disc hemorrhage during the follow-up (P = 0.013) were significant factors associated with faster global RNFL thinning. Larger CMvD width relative to RMvI width may be indicative of an increased risk of faster RNFL thinning in POAG with localized RNFL defect. Comparing the microvasculature impairment in individual layers may help predict more rapid glaucoma progression.

Influence of choroidal microvasculature dropout on progressive retinal nerve fibre layer thinning in primary open-angle glaucoma: comparison of parapapillary β-zones and γ-zones

Background/aimsTo compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary β-zones and γ-zones.Methods294 eyes with primary open-angle glaucoma...

Risk of Normal Tension Glaucoma Progression From Automated Baseline Retinal-Vessel Caliber Analysis: A Prospective Cohort Study

To determine the relationship between baseline retinal-vessel calibers computed by a deep-learning system and the risk of normal tension glaucoma (NTG) progression. Prospective cohort study. Three hundred and ninety eyes from 197 patients with NTG were followed up for at least 24 months. Retinal-vessel calibers (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]) were computed from fundus photographs at baseline using a previously validated deep-learning system. Retinal nerve fiber layer (RNFL) thickness and visual field (VF) were evaluated semiannually. The Cox proportional-hazards model was used to evaluate the relationship of baseline retinal-vessel calibers to the risk of glaucoma progression. Over a mean follow-up period of 34.36 ± 5.88 months, 69 NTG eyes (17.69%) developed progressive RNFL thinning and 22 eyes (5.64%) developed VF deterioration. In the multivariable Cox regression analysis adjusting for age, gender, intraocular pressure, mean ocular perfusion pressure, systolic blood pressure, axial length, standard automated perimetry mean deviation, and RNFL thickness, narrower baseline CRAE (hazard ratio per SD decrease [95% confidence interval], 1.36 [1.01-1.82]) and CRVE (1.35 [1.01-1.80]) were associated with progressive RNFL thinning and narrower baseline CRAE (1.98 [1.17-3.35]) was associated with VF deterioration. In this study, each SD decrease in the baseline CRAE or CRVE was associated with a more than 30% increase in the risk of progressive RNFL thinning and a more than 90% increase in the risk of VF deterioration during the follow-up period. Baseline attenuation of retinal vasculature in NTG eyes was associated with subsequent glaucoma progression. High-throughput deep-learning-based retinal vasculature analysis demonstrated its clinical utility for NTG risk assessment.

Smoking and progressive retinal nerve fibre layer thinning in glaucoma

Background/AimsTo investigate the relationship between smoking and smoking intensity, and the rate of retinal nerve fibre layer (RNFL) thinning in patients with primary open angle glaucoma (POAG).MethodsIn this longitudinal study,...

Inter-eye correlation analysis of 24-h IOPs and glaucoma progression

PurposeTo determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters.MethodsWe extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP(Tavg), IOP variation (IOPvar), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships.ResultsTwo hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52% of eyes with RNFL progression data showed disease progression. There was no significant difference in Tmax, Tavg, and IOPvar between progressors and non-progressors (all p > 0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant and Tmax, Tavg, and IOPvar. Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak.ConclusionIn line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.

Long-term Effect of Permanent Demyelination on Axonal Survival in Multiple Sclerosis.

Background and ObjectivesTo investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).MethodsOnly patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits. Low-contrast visual acuity (LCVA) was also evaluated at baseline and follow-up. Patients were examined twice with an average interval of 6.1 ± 1.4 years.ResultsFrom 85 examined patients with multiple sclerosis, 28 satisfied inclusion criteria. Latency of the mfVEP was delayed, and RNFL thickness was reduced in ON eyes compared with fellow eyes at both visits. There was significant correlation between latency asymmetry and baseline or follow-up intereye RNFL thickness asymmetry. Intereye asymmetry of LCVA at baseline correlated with baseline latency asymmetry of mfVEP and baseline asymmetry of RNFL thickness. Latency of the mfVEP in ON eyes improved slightly during the follow-up period, whereas latency of the fellow eye remained stable. By contrast, RNFL thickness significantly declined in both ON and fellow eyes during the follow-up period. The rate of RNFL thinning in ON eyes, however, was more than 2 times faster compared with the fellow eyes (p < 0.001). Furthermore, baseline latency asymmetry significantly correlated with the rate of RNFL thinning in ON eyes during the follow-up (p < 0.001), explaining almost half of the variability of temporal RNFL progression. For each millisecond of latency delay (i.e., ∼0.5 mm of demyelination along the optic nerve), temporal RNFL thickness was annually reduced by 0.05%.DiscussionOur study provides clear in vivo evidence that chronic demyelination significantly accelerates axonal loss. However, because this process is slow and its effect is mild, long-term monitoring is required to establish and confidently measure the neurodegenerative consequences of demyelination.

Predictors of Retinal Nerve Fiber Layer Parameters Following Scleral Buckling Surgery in Primary Rhegmatogenous Retinal Detachment.

Objective: This study aimed to examine predictors of retinal nerve fiber layer (RNFL) parameters following scleral buckling (SB) surgery for primary rhegmatogenous retinal detachment (RRD) and to determine the influence of the magnitude of change in qualitative and quantitative parameters on RNFL.Methods: In an observational prospective study, 40 subjects who underwent successful retinal reattachment with SB surgery done within one month of RRD were evaluated for the parameters of best-corrected visual acuity (BCVA), refractive error, intraocular pressure (IOP), axial length (AL), anterior chamber depth (ACD), angle opening distance (AOD 500 and AOD 750), trabecular iris surface area (TISA 500 and TISA 750), visual fields, and ganglion cell count (GCC) and RNFL before and three months after SB. We additionally noted qualitative factors like extent, location, and type of buckle; phakic status; and grade of proliferative vitreoretinopathy in the affected eye. The change in value of quantitative parameters was found. The influence of baseline values and magnitude of change of quantitative and qualitative parameters on average RNFL thickness and magnitude of change of RNFL thickness after SB was found.Results: Post-SB, average RNFL thickness reduced from 108.58±20.38 microns to 103.73±17.98 microns (p =0.042). The baseline temporal upper (TU), temporal lower (TL), and nasal lower (NL) RNFL thickness (p=0.01, p=0.02, p=0.01, respectively) and total deviation (TD) values of visual fields (p=0.01) correlated positively while baseline GCC gross loss of volume (p=0.01) correlated negatively with post-operative RNFL thickness. The TU, TL, and NL RNFL thickness (p=0.04, p=0.01, p=0.01, respectively) and average GCC (p=0.04) correlated negatively with the magnitude of change in RNFL. The magnitude of change in baseline parameters after surgery was correlated with the magnitude of change in average RNFL thickness. It was noticed that change in AL (p<0.01), TISA 500 (p=0.02), TISA 750 (p<0.01), GCC focal loss of volume (p=0.02), and temporal RNFL thickness (p<0.01) correlated positively while the change in refractive error correlated negatively (p=0.04). Except for the grade of proliferative vitreoretinopathy (PVR) (p=0.04), none of the qualitative parameters, including extent, type, and location of the buckle; and phakic status, had a significant association with post-operative average RNFL thickness or magnitude of its change.Conclusions: The predictors of average RNFL thickness following SB include AL; myopic shift; TISA; visual fields TD; average, TU, TL, and NL RNFL thickness; average GCC, gross and focal loss of volume; and grade of PVR. So an early surgery to prevent preoperative ganglion cell and RNFL loss and progression of PVR is recommended.

Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial

BackgroundWhereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo.MethodsThis is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models.DiscussionOutcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups.Trial registrationChinese Clinical Trial Registry 1900021998

Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich’s Ataxia

Ocular abnormalities occur frequently in Friedreich’s ataxia (FRDA), although visual symptoms are not always reported. We evaluated a cohort of patients with FRDA to characterise the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). A total of 48 patients from 42 unrelated families were recruited. Mean age at onset was 13.8 years (range 4–40), mean disease duration 19.5 years (range 5–43), mean disease severity as quantified with the Scale for the Assessment and Rating of Ataxia 22/40 (range 4.5–38). All patients displayed variable ataxia and two-thirds had ocular abnormalities. Statistically significant thinning of average retinal nerve fibre layer (RNFL) and thinning in all but the temporal quadrant compared to controls was demonstrated on OCT. Significant RNFL and macular thinning was documented over time in 20 individuals. Disease severity and visual acuity were correlated with RNFL and macular thickness, but no association was found with disease duration. Our results highlight that FDRA is associated with subclinical optic neuropathy. This is the largest longitudinal study of OCT findings in FRDA to date, demonstrating progressive RNFL thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA.

Progressive Vessel Density Reduction on OCT Angiography in Glaucoma Eyes with Disc Hemorrhages

To identify longitudinal changes in peripapillary and parafoveal vessel density (VD) measured by OCT angiography (OCTA) in primary open-angle glaucoma (POAG) eyes with disc hemorrhages (DHs). Prospective cohort study conducted from August 2016 through August 2020 PARTICIPANTS: Eighteen Asian-Indian participants with POAG (18 eyes) who sought treatment at the clinic with a single DH in the peripapillary region were recruited consecutively. The study was conducted at a tertiary eye care center. All participants who were recruited underwent a baseline OCT and OCTA, which were repeated every 4 to 6 months. Peripapillary VD and retinal nerve fiber layer (RNFL) thickness, parafoveal VD and ganglion cell-inner plexiform layer (GCIPL) thickness in the DH sector, and the corresponding mirror-image sector across the horizontal meridian (control) were evaluated over time using linear mixed-effects models. The baseline average RNFL thickness was 79 ± 9 μm. Mean duration of follow-up was 2.6 ± 0.7 years. In the DH sector, all VD and structural parameters showed a significant negative slope (P < 0.01). In the control sector, the slopes of the structural parameters (RNFL and GCIPL thickness) were not significant (P>0.05), but the rate of change of the peripapillary and parafoveal VDs were significant (P < 0.01). The rate of change of peripapillary VD was greater in the DH sector compared with the non-DH sector (-2.86 ± 0.6%/year vs. -1.71 ± 0.7%/year; P < 0.01). However, the parafoveal VD slopes did not differ significantly between DH and control sectors (-2.9 ± 0.17%/year vs. -2.8 ± 0.8%/year; P= 0.51). Eyes with POAG harboring a DH showed not only progressive RNFL and GCIPL loss in the DH sector, but also progressive peripapillary and parafoveal VD reduction in the DH and non-DH regions as documented on OCTA.

Intraocular Pressure Control Predicts Retinal Nerve Fiber Layer Thinning in Primary Angle Closure Disease: The CUPAL Study

To determine the relationship of intraocular pressure (IOP) control with subsequent retinal nerve fiber layer (RNFL) thinning in patients with primary angle closure disease (PACD). Prospective cohort study. The study monitored 517 treated PACD eyes from 280 Chinese patients at least 24 months. IOP was measured every 3 months using Goldmann applanation tonometry, and RNFLs were measured by spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering) every 6 months. IOP mean and fluctuation were calculated as the average and the coefficient of variation of IOP measurements during the first 18 months of the study period. The relationship between IOP and subsequent RNFL changes over time were examined using multivariable linear mixed models. Intraclass correlations at the patient and eye levels were also controlled using nested random intercepts in the models. IOP mean (β=-1.20 µm/y per 1 mm Hg, P < .001) and IOP fluctuation (β=-3.10 µm/y per 10% unit change in the coefficient of variation, P < .001) were independently negatively associated with subsequent progressive global RNFL changes, after adjustment for age, sex, and baseline RNFL thickness. In the sectoral analysis, both higher mean IOP and IOP fluctuation predicted progressive RNFL thinning in the inferotemporal, superotemporal, superonasal, and temporal sectors in the order of strength of association. In the subgroup analysis by disease category, IOP fluctuation showed greater association with global RNFL thinning in eyes with primary angle closure glaucoma (P=.010) than in eyes without glaucomatous changes (P=.07). In treated PACD eyes, large IOP fluctuation is an independent predictor for subsequent progressive RNFL thinning in addition to high mean IOP during follow-up.

Optical Microangiography and Progressive Retinal Nerve Fiber Layer Loss in Primary Open Angle Glaucoma

To evaluate the association between optical microangiography (OMAG) measurements and progressive retinal nerve fiber layer (RNFL) loss in primary open angle glaucoma (POAG). Prospective case series. Sixty-four eyes of 40 patients with POAG (108 quadrants) with mild to moderate functional damage were longitudinally studied for at least 2 years and with a minimum of 3 optical coherence tomography examinations. OMAG imaging was performed at the baseline visit. Effect of clinical parameters (age, sex, presence of systemic diseases, central corneal thickness, presence of disc hemorrhage, and mean and fluctuation of intraocular pressure during follow-up), baseline hemifield mean deviation, baseline quadrant optical coherence tomography RNFL and ganglion cell inner plexiform layer thickness), and OMAG (peripapillary and macular perfusion density [PD] and vessel density [VD]) on the rate of RNFL change was evaluated using linear mixed models. Average (±SD) mean deviation, RNFL, and ganglion cell inner plexiform layer thickness of the analyzed quadrants at baseline were -5.5 ± 2.9 dB, 96.5 ± 17.9 µm, and 73.8 ± 8.6 µm, respectively. Peripapillary PD and VD in the quadrant were 44.6% ± 5.9% and 17.5 ± 2.2 mm/mm2, respectively. Rate of quadrant RNFL change was -1.8 ± 0.6 µm/y. Multivariate mixed models showed that lower peripapillary PD (coefficient=0.08, P=.01) and lower VD (coefficient=0.21, P=.02) were significantly associated with a faster rate of RNFL loss. Lower baseline peripapillary PD and VD measured using OMAG were significantly associated with a faster rate of RNFL loss in POAG. OMAG imaging provides useful information about the risk of glaucoma progression and the rate of disease worsening.

Detection of Primary Angle Closure Glaucoma Progression by Optical Coherence Tomography.

To compare the role of spectral-domain optical coherence tomography (SD-OCT) in regard to retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) assessment in the detection of primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) progression. In the prospective study, 131 subjects with PACG and POAG were examined during 72 months with follow-up visits every 6 months. Visual field (VF) progression was detected using the Guided Progression Analysis (GPA) of the Humphrey visual field analyzer and structural change using SD-OCT while a significant negative trend for the RNFL and GCC was gauged. The diagnostic accuracy of RNFL and GCC thinning in the detection of glaucoma progression was compared between PACG and POAG eyes using the Kaplan-Meier method with the calculation of the log-rank test. Progression was detected in 57% of eyes with POAG and 59% of eyes with PACG. The rate of thinning of RNFL (-2.95±1.85 μm/y) and GCC (-3.22±2.96 μm/y) was significantly higher in PACG progression eyes compared with POAG [-1.64±2.00 μm/y (P=0.018) and -1.74±2.05 μm/y (P=0.046), respectively]. The progression was associated with initial pattern standard deviation in both glaucoma subtypes, while only in PACG-with long-term intraocular pressure fluctuations (cutoff >5.2 mm Hg) and lens thickness (cutoff >4.92 mm), and only in POAG-with initial focal loss volume of GCC (cutoff >1.5%).In PACG, the rate of the visual function deterioration correlated with GCC thinning rate (r=0.330, P=0.027), but not with the RNFL thinning rate (r=-0.010, P=0.79), while in POAG, it was significant for both RNFL thinning (r=0.296, P=0.039) and GCC thinning (r=0.359, P=0.011). In PACG patients with progressive GCC thinning, functional progression was detected earlier (log-rank test P≤0.001) than in patients with progressive RNFL thinning (log-rank test P=0.457), while for POAG, these results were P=0.012 and ≤0.001 for GCC and RNFL thinning, respectively. SD-OCT plays an important role in detecting PACG progression. In contrast to POAG, GCC thinning predicted functional loss better than RNFL thinning in PACG.