Rate Of Retinal Nerve Fiber Layer Thinning Research Articles

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.

The Impact of Achieving Target Intraocular Pressure on Glaucomatous Retinal Nerve Fiber Layer Thinning in a Treated Clinical Population

To estimate the effect of being below and above the clinician-set target intraocular pressure (IOP) on rates of glaucomatous retinal nerve fiber layer (RNFL) thinning in a treated real-world clinical population. Retrospective cohort study. A total of 3256 eyes (1923 patients) with ≥5 reliable optical coherence tomography scans and 1 baseline visual field test were included. Linear mixed-effects modeling estimated the effects of the primary independent variables (mean target difference [measured IOP - target IOP] and mean IOP, mm Hg) on the primary dependent variable (RNFL slope, µm/y) while accounting for additional confounding variables (age, biological sex, race, baseline RNFL, baseline pachymetry, and disease severity). A spline term accounted for differential effects when above (target difference >0 mm Hg) and below (target difference ≤0 mm Hg) target pressure. Eyes below and above target had significantly different mean RNFL slopes (-0.44 vs -0.71 µm/y, P < .001). Each 1 mm Hg increase above target had a 0.143 µm/y faster rate of RNFL thinning (P < .001). Separating by disease severity, suspect, mild, moderate, and advanced glaucoma had 0.135 (P = .002), 0.116 (P = .009), 0.203 (P = .02), and 0.65 (P = .22) µm/y faster rates of RNFL thinning per 1 mm Hg increase, respectively. Being above the clinician-set target pressure is associated with more rapid RNFL thinning in suspect, mild, and moderate glaucoma. Faster rates of thinning were also present in advanced glaucoma, but statistical significance was limited by the lower sample size of eyes above target and the optical coherence tomography floor effect.

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.

Normotensive Glaucoma in the Fellow Eye of Patient with Unilateral Pseudoexfoliation

To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (-1.88 ± 2.83 μm/year) compared with the control group (-0.27 ± 5.29 μm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, -0.33 ± 0.90 dB/year; control group, -0.11 ± 0.84 dB/year; p = 0.236). NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.

Longitudinal Choriocapillaris Vascular Density Changes in Different Types of Primary Open-Angle Glaucoma.

To evaluate longitudinal changes in choriocapillaris perfusion in patients with glaucoma with four phenotypes of optic disc damage and to explore associated factors with decreased choriocapillaris vessel density (CVD). This prospective longitudinal study included 96 eyes of 96 patients with primary open-angle glaucoma (POAG). Patients with POAG was differentiated into the optic disc phenotypes of focal ischemic type (FI), myopic type (MY), senile sclerotic type (SS), and generalized enlargement type (GE). Patients were followed up every three months. Simple linear regression was used to investigate the factors associated with a reduction in CVD. The median follow-up time was 2.5 years (range, 2.0-3.0 years). Choriocapillaris perfusion tended to decrease over time, with CVD decreasing significantly faster in the FI type than in the other three types (P < 0.001). The percentage decrease in the FI type was 7.85%, 10.89%, and 8.88% faster than MY, SS and GE, respectively, after correcting for age, gender, axial length, intraocular pressure, mean deviation, retinal nerve fiber layer (RNFL), and image quality score. In multivariate regression, decreased CVD was independently associated with the rate of RNFL thinning. FI type had the fastest rate of CVD decline in the four phenotypes of optic disc damage, and decreased CVD was positively correlated with the rate of RNFL thinning. The role of the choriocapillaris in the pathogenesis and therapeutic potential of glaucoma require further attention to facilitate better management of glaucoma patients.

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.

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

Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma

To investigate the relationship between the rate of retinal nerve fiber layer (RNFL) loss during initial follow-up and the magnitude of associated visual field loss during an extended follow-up period. Retrospective cohort study. A total of 1,150 eyes of 839 glaucoma patients extracted from the Duke Glaucoma Registry. Rates of RNFL loss were obtained from global RNFL thickness values of the first 5 optical coherence tomography (OCT) scans. Rates of visual field loss were assessed using standard automated perimetry mean deviation (SAP MD) during the entire follow-up period. Joint longitudinal mixed effects models were used to estimate rates of change. Eyes were categorized as fast, moderate or slow progressors based on rates of RNFL loss, with cutoffs of ≤-2 µm/year, -2 to -1 µm/year and ≥-1 µm/year, respectively. Univariable and multivariable regressions were completed to identify significant predictors of SAP MD loss. The rate of RNFL change was -0.76±0.85 µm/y during initial follow-up, which occurred over 3.7±1.5 years. 765 (66%) eyes were slow, 328 (29%) moderate, and 57 (5%) fast progressors, with rates of RNFL thinning of -0.36±0.54 µm/year, -1.34±0.25 µm/year, and -2.87±1.39 µm/year respectively. The rates of SAP MD loss among slow, moderate, and fast OCT progressors were -0.16±0.35 dB/y, -0.32±0.43 dB/y, and -0.71±0.65 dB/y respectively over the extended follow-up period of 6.1±1.9 years (P<0.001). Age, OCT progressor group, and concurrent SAP rate were all significantly associated with the overall rate of SAP MD loss in a multivariable model (all P<0.001). Rapid RNFL thinning during an initial follow-up period was predictive of concurrent and subsequent rates of visual field decline over an extended period.

Juxtapapillary Deep-Layer Microvasculature Dropout and Retinal Nerve Fiber Layer Thinning in Glaucoma

We sought to characterize juxtapapillary (JP) and non-JP microvasculature dropout in patients with primary open-angle glaucoma and to compare their rate of retinal nerve fiber layer (RNFL) thinning. Retrospective cohort study. A total of 141 eyes with primary open-angle glaucoma with ≥4 serial optical coherence tomography (OCT) images after initial OCT angiography for ≥2 years were included. Based on OCT angiography imaging, the 3 groups were matched by age and visual field mean deviation: JP group (parapapillary deep-layer microvasculature dropout in contact with the optic disc boundary, n=47), non-JP group (dropout not reaching the optic disc boundary, n=47), and no-dropout group (lacking the dropout, n=47). The RNFL thinning rate was compared among the 3 groups. The rate of RNFL thinning tended to be fastest in the JP group followed by the non-JP group and no-dropout group in all areas except the temporal and nasal sectors. Post hoc analysis revealed that the JP group had significantly faster RNFL thinning than did the no-dropout group in the global area and the inferotemporal and inferonasal sectors (P < .05). When subgroup analysis was performed for subjects in which the main sector of dropout was the inferotemporal sector, the JP group had significantly faster RNFL thinning than the other 2 groups in the corresponding inferotemporal sector (P < .001). Eyes with JP microvasculature dropout showed faster RNFL thinning than eyes without dropout. These findings suggest that deep-layer microvasculature dropout, especially in contact with the optic disc boundary, is associated with rapid glaucoma progression.

Rates of RNFL Thinning in Patients with Suspected or Confirmed Glaucoma Receiving Unilateral Intravitreal Injections for Exudative AMD

This study evaluated whether the rate of retinal nerve fiber layer (RNFL) thinning is faster in eyes receiving intravitreal injections than in fellow uninjected eyes among patients suspected of having or confirmed to have glaucoma and exudative age-related macular degeneration (AMD). Retrospective comparative cohort study. Patients with a diagnosis of unilateral exudative AMD and confirmed to have or suspected of having glaucoma in both eyes receiving unilateral intravitreal injections were identified. Those with ≥3 RNFL optical coherence tomography scans and ≥6 injections were included in the study. Rates of RNFL thinning in the injected eye versus the uninjected eye were estimated using linear mixed models. The main outcome measurement was the differences in rates of RNFL thinning in the injected versus the fellow uninjected eye. The effects of postinjection elevation of intraocular pressure (IOP), injection frequency, and number of injections were also evaluated. A total of 53 patients met the inclusion criteria, receiving 26.4 ± 15.9 intravitreal injections. The average rate of RNFL thinning in uninjected eyes was-0.620μm/year (P= .029). Injected eyes had an additional incremental loss of-0.385μm/year, but this value was not statistically significant (95% confidence interval [CI]:-1.147 to 0.379μm/year; P= .324). Subgroup analysis with only glaucoma patients (n= 33) also demonstrated a nonsignificant effect of injections (-0.568μm/year; 95% CI:-1.454 to 0.319μm/year; P= .212). Postinjection IOP elevation, injection frequency, and total number of injections were not associated with faster RNFL loss. Among exudative AMD patients with glaucoma or suspected of having glaucoma, the rate of RNFL thinning in eyes receiving intravitreal injections did not significantly differ from that of fellow uninjected eyes.

Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes

To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes. Prospective, longitudinal study. Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results. Baseline corneal SPs were measured using Corvis ST (Oculus Optikgeräte GmbH). Participants were followed up every 6 months with clinical examination, HVF testing, and OCT. The baseline SP at first applanation (SP-A1) and highest concavity predicted the prospective outcome measures. Structural progression was measured by the OCT rate of thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL). Functional progression was assessed by permutation analysis of pointwise linear regression criteria on HVF testing. Stiffness parameters correlated positively with central corneal thickness (CCT), which was adjusted for in all analyses. A higher SP-A1, suggestive of a stiffer cornea, was associated with a faster rate of RNFL thinning (P < 0.001), synergistic with thinner CCT (P= 0.004) over a mean follow-up of 4.2 years. Eyes with higher SP-A1 and thinner CCT (thin and stiff corneas) showed accelerated RNFL thinning by 0.72 μm/year relative to eyes with lower SP-A1 and thicker CCT (95% confidence interval [CI], 0.17-1.28; P= 0.011) and were at 2.9-fold higher likelihood of fast RNFL progression of more than 1 μm/year (95% CI, 1.4-6.1; P= 0.006). Consistent results also were observed with GCIPL thinning. Furthermore, a higher SP-A1 was associated with a greater risk of visual field progression (P= 0.002), synergistic with thinner CCT (P= 0.010). Eyes with higher SP-A1 and thinner CCT were at 3.7-fold greater risk of visual field progression relative to eyes with thicker CCT and lower SP-A1 (95% CI, 1.3-10.5; P= 0.014). Glaucoma suspect eyes with higher corneal SPs and lower CCT, suggestive of thin and stiff corneas, are at greater risk of progression. Corneal SPs seem to act synergistically with CCT as risk factors for glaucoma progression.

Utility of Optical Coherence Tomography in the Diagnosis and Management of Optic Neuropathy in Patients with Fibrous Dysplasia.

Optic neuropathy (ON) is a highly disabling complication of fibrous dysplasia (FD). The optimal test for identifying and monitoring ON in FD is unknown. Optical coherence tomography (OCT) is an imaging modality that detects retinal nerve fiber layer (RNFL) thinning, a sign of optic nerve atrophy. The purpose of this study was to (i) assess the ability of OCT RNFL thickness measurements to identify ON in FD; (ii) compare the performance of RNFL thickness to computed tomography measurements; and (iii) examine changes in RNFL thickness over time to assess disease progression. A retrospective cohort study was performed to assess subjects (n = 70) who underwent neuro-ophthalmologic examination, including OCT. The diagnostic utility of RNFL thickness was determined using receiver operator characteristic (ROC) curve analysis, and the accuracy was compared with computed tomography measurements. The relationship between RNFL thickness and age was assessed cross-sectionally, using generalized estimating equation methodology, and longitudinally, using a generalized mixed model. Eleven subjects were identified with ON. RNFL thickness identified ON (area under curve = 0.997, p < 0.0001) with sensitivity and specificity of 100% and 95%, respectively, when using the diagnostic criterion of ≤71 μm. RNFL thickness outperformed computed tomography measurements of optic canal narrowing and optic nerve stretch. Subjects with ON exhibited a greater decrease in RNFL thickness with each year of age (-0.70 μm/year, p < 0.001) than subjects with normal vision (-0.16 μm/year, p < 0.05). When assessed longitudinally, subjects with normal vision demonstrated an increase in RNFL thickness until approximately age 20 years that decreased thereafter. In contrast, subjects with ON exhibited an earlier decrease in RNFL thickness during adolescence. In conclusion, RNFL thickness of ≤71 μm accurately identified ON in this population. By establishing the difference in rate of RNFL thinning in patients with and without ON, clinicians may distinguish between patients at risk for ON and intervene before irreversible damage. © 2020 American Society for Bone and Mineral Research.

Trends in the Retinal Nerve Fiber Layer Thickness Changes with Different Degrees of Visual Field Defects.

Purpose To explore the disease progression of primary open-angle glaucoma (POAG) in individuals with different degrees of VF defects by analyzing the trends in retinal nerve fiber layer (RNFL) changes at each stage. Methods A total of 39 patients (77 eyes) were divided into three groups based on the severity of glaucomatous visual field (VF) loss: the first group included patients with mild baseline VF defects (mild group; n = 21 eyes). The second group included patients with moderate VF defects (moderate group; n = 18 eyes). The third group included patients with severe baseline VF defects (severe group; n = 38 eyes). For all patients, slit-lamp biomicroscopy of the anterior and posterior segments and detailed fundus and optic disc inspections were performed, the intraocular pressure (IOP) was measured by Goldman tonometry, best-corrected visual acuity (BCVA) was measured, the RNFL thickness was measured by OCT, and the VF was assessed by the Octopus perimeter. All the groups were followed up postoperatively for 18 months. Results The mean RNFL thickness was recorded for all the visits. Using simple linear regression analysis, we found that the R2 values of the three groups were 0.988, 0.982, and 0.814, respectively, and the slopes of mean RNFL thickness changes for mild, moderate, and severe baseline VF defects were −0.088, −0.082, and −0.015, respectively. Moreover, we used simple linear regression analysis to explore whether and how the speed of RNFL thinning differs across groups. The R2 values of the three groups were 0.982, 0.978, and 0.805, respectively, and the slopes for mild, moderate, and severe baseline VF defects were 0.089, 0.085, and 0.017, respectively. Conclusion The rate of RNFL thinning is linear; RNFL thinning is the fastest in individuals with mild baseline VF defects, followed by those with moderate baseline VF defects. In individuals with severe VF defects, changes in the RNFL thickness do not appropriately reflect the progression of the disease. The clinical trial is registered with ChiCTR2000028975.

Association between Rates of Retinal Nerve Fiber Layer Thinning after Intraocular Pressure–Lowering Procedures and Disc Hemorrhage

To compare the rates of retinal nerve fiber layer (RNFL) thinning after intraocular pressure (IOP) lowering procedures in eyes with or without disc hemorrhage (DH) history. Observational cohort study. A total of 166 primary open angle glaucoma (POAG) eyes and glaucoma suspect eyes (37 eyes with DH history (DH group) and 129 eyes without DH (non-DH group)) were included from the African Decent and Glaucoma Evaluation Study (ADAGES) and the Diagnostic Innovations in Glaucoma Study (DIGS). Subjects underwent stereoscopic optic disc photography annually and spectral-domain optical coherence tomography (OCT) RNFL thickness measurements every 6 months. The rates of RNFL thinning were compared in eyes with and without DH using univariate and multivariable linear mixed effects models. The rates of RNFL thinning. The mean follow-up of DH group and non-DH group was 4.6 years and 4.2 years, respectively. DH group had more procedures (2.4 vs. 1.9, P= 0.080) before follow-up, and more medications (1.8 vs. 1.4, P= 0.052) and lower mean IOP (12.69 mmHg vs. 14.41 mmHg, P= 0.012) during follow-up compared to non-DH group. When mean IOP was adjusted as a covariate in the model, the RNFL thinning rate in the DH group was 2-fold faster than in the non-DH group (-0.61 μm /year vs. -0.33 μm /year, P= 0.025). Higher mean IOP during follow-up was associated with a faster rate of RNFL thinning after procedures. POAG or glaucoma suspect eyes with a history of DH should be carefully followed after IOP-lowering procedures. Additional IOP-lowering may be needed to slow structural progression of the DH eyes to the same rate as the non-DH eyes.

Influence of Choroidal Microvasculature Dropout on the Rate of Glaucomatous Progression: A Prospective Study

To determine the prognostic significance of choroidal microvasculature dropout (MvD) to predict the future rate of progressive retinal nerve fiber layer (RNFL) thinning in eyes with primary open-angle glaucoma (POAG). Prospective, longitudinal case series. This study enrolled 101 eyes of 101 patients with POAG who underwent OCT angiography (OCTA) imaging of the optic nerve head at baseline and were followed up for at least 2 years thereafter, during which RNFL thickness was measured by serial spectral-domain OCT. The peripapillary microvasculature was evaluated by examining en face OCTA images. Choroidal MvD was defined as a focal sectoral capillary dropout with no visible microvascular network in the choroidal layer. The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements. Influence of the presence of an MvD on the rate of subsequent RNFL thinning. Microvasculature dropout was identified in 48 eyes (47.5%). The rate of global RNFL thinning was significantly faster in eyes with MvD than eyes without MvD (-1.6±0.8 vs.-1.2±0.9 μm/year, P= 0.018). Eyes with MvD in the inferior hemisphere (n= 41) showed a faster rate of inferior RNFL thinning than eyes without MvD (P= 0.036). Eyes with MvD in both the superior and inferior hemispheres (n= 5) showed faster rates of superior (P= 0.027) and inferior (P= 0.016) RNFL thinning than eyes without MvD. Multivariate regression analysis showed that MvD at baseline (P= 0.003) and the presence of disc hemorrhage during follow-up (P= 0.001) were independently associated with a faster rate of global RNFL thinning. Microvasculature dropout was an independent predictor of a faster rate of progressive RNFL thinning in patients with POAG. Microvasculature dropout location was topographically associated with the location of faster RNFL thinning.

Elucidation of the Strongest Factors Influencing Rapid Retinal Nerve Fiber Layer Thinning in Glaucoma.

To determine which groupings of prognostic factors best explain the rapid progressive retinal nerve fiber layer (RNFL) thinning in patients with primary open-angle glaucoma (POAG). Optic nerves of 111 POAG patients who were followed for at least 2.5 years, during which the RNFL thickness was measured by serial spectral-domain optical coherence tomography (OCT) were included. Eyes were imaged using enhanced depth-imaging spectral-domain OCT and swept-source OCT angiography to determine the lamina cribrosa curvature index (LCCI), and the presence of a choroidal microvasculature dropout (cMvD), respectively. The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements. A regression tree model was used to find groupings of factors that best explain the rate of future RNFL thinning. Disc hemorrhage, larger LCCI, and presence of cMvD were associated with faster global RNFL thinning in the multivariate regression analysis. The regression tree analysis revealed three stratified groups based on the rate of RNFL thinning, divided by the LCCI and the presence of cMvD. Eyes with LCCI ≥11.87 had the fastest RNFL thinning (-2.4 ± 0.8 μm/year, mean ± SD). Among eyes with LCCI <11.87, the presence of cMvD was the strongest factor influencing faster RNFL thinning (-1.5 ± 0.8 μm/year). Eyes with LCCI <11.87 and without a cMvD exhibited the slowest RNFL thinning (-0.8 ± 0.9 μm/year). Our regression tree model demonstrated that larger LCCI, and then the presence of cMvD were the first and second strongest prognostic factors for faster progressive RNFL thinning. Further studies may be needed to confirm these findings.

Evaluation of Parapapillary Choroidal Microvasculature Dropout and Progressive Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma

Parapapillary choroidal microvasculature dropout (MvD) is considered one of pathophysiological manifestations of glaucomatous damage. To evaluate the longitudinal change in the parapapillary choroidal MvD in patients with primary open-angle glaucoma (POAG), and to determine whether this change is associated with progressive retinal nerve fiber layer (RNFL) thinning. This prospective observational case series was conducted at a tertiary referral center in Korea and included 68 patients with POAG who exhibited parapapillary choroidal MvD in en face optical coherence tomography (OCT) angiography (OCTA) images who were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2016, through July 31, 2018. The mean (SD) follow-up period was 2.5 (0.2) years and observers were masked to the clinical characteristics of the participants for measurements. The OCTA images were obtained twice at an interval of at least 2 years, during which the RNFL thickness was measured at least 4 times in serial OCT examinations. Microvasculature dropout was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. The MvD area was measured in the OCTA images obtained at the baseline and the final follow-up. The significance of changes in the MvD area was defined using the 95% Bland-Altman limits of agreement. The rate of RNFL thinning was determined by linear regression of the serial OCT RNFL thickness measurements. The association between the change in the MvD area and the rate of RNFL thinning. Of 68 Korean participants, 37 (54.5%) were women, and the mean (SD) age was 54.3 (13.1) years. Among 68 eyes, 22 (32.4%) showed increases in the MvD area during the follow-up. Faster global RNFL thinning was associated with a larger baseline parapapillary atrophy β-zone (β = -0.55; 95% CI, -0.96 to -0.14; P = .01), disc hemorrhage detection during the follow-up period (β = -0.75; 95% CI, -1.67 to -0.34; P = .001), and a larger increase in the MvD area (β = -4.74; 95% CI, -7.72 to -1.75; P = .002). The MvD area was not associated with the rate of RNFL thinning at baseline or the final follow-up. Microvasculature dropout enlargement was associated with progressive RNFL thinning in POAG.

Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma

Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] μm/y; difference, -0.43 [-0.76 to -0.09] μm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] μm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (β2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (β2, -0.05 [95% CI, -0.17 to 0.06], P = .36). These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

Relationship between the rate of change in lamina cribrosa depth and the rate of retinal nerve fiber layer thinning following glaucoma surgery.

PurposeTo assess whether lamina cribrosa depth (LCD) reduction and the rate of change in LCD over time (ΔLCD/Δt) is associated with retinal nerve fiber layer (RNFL) thickness and the rate of RNFL thinning over time (ΔRNFL/Δt) to test the hypothesis that, in a long term, RNFL thinning occurs irrespectively to the displacement of the lamina cribrosa following glaucoma surgery.MethodsTwenty-nine primary open-angle glaucoma patients underwent glaucoma surgery. Sixteen patients underwent trabeculectomy and 13 patients undertook non-penetrating deep sclerectomy. Images of optic nerve head using spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging technology were obtained preoperatively, at one-, three-, six-month and follow-up postoperative visit from 12 to 29 months after surgery (1pv, 3pv, 6pv, and FUpv, respectively). Correspondingly, measurements of the circumpapillary RNFL thickness were acquired.ResultsIntraocular pressure decreased from 24.0±8.9 to 10.9±3.9mmHg at 6pv (P<0.001) and to 12.7±4.4mmHg at FUpv (P<0.001). LCD was reduced from 465.3±136.4μm to 402.9±126.4μm at 1pv (P<0.001) and maintained similar position at 6pv (394.3±118.4μm; P = 0.170 with respect to 1pv). A significant decrease in the LCD was noted at FUpv (342.8±90.3μm, P<0.001) with respect to 6pv. RNFL thickness increased significantly to 64.9±19.8μm at 1pv (P = 0.005) and subsequently decreased to baseline level at 3pv. Further statistically significant decrease in RNFL thickness with respect to previous visit was found at 6pv and at FUpv (56.4±15.6μm and 55.0±14.0μm, P = 0.023 and P = 0.045, respectively). A thinner RNFL thickness at FUpv was not related to the LCD at FUpv (P = 0.129) but was correlated with ΔLCD/Δt at FUpv (P = 0.003). The ΔRNFL/Δt at FUpv was statistically significantly correlated with ΔLCD/Δt at FUpv (P<0.001).ConclusionsThis is the first study that considers direct correlation between the rate of change in LCD with the rate of RNFL thinning over time. A thinner RNFL thickness following glaucoma surgery was associated with the rate of LCD reduction, not with position of the lamina cribrosa at the FUpv.

Association between Rates of Retinal Nerve Fiber Layer Thinning and Previous Disc Hemorrhage in Glaucoma

To investigate the relationship between previous disc hemorrhage (DH) and subsequent rates of retinal nerve fiber layer (RNFL) thinning. Longitudinal, observational cohort study. Twenty-eight patients with glaucoma and patients with suspected glaucoma who had a history of DH in 1 eye (unilateral DH), but not in the fellow eye, enrolled in the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study were included. All subjects underwent annual optic disc photography and semiannual spectral-domain OCT RNFL thickness measurements. Multivariable linear mixed-effects models were used to investigate the relationship between the presence of previous DH and RNFL thinning rates while adjusting for potential confounding factors, such as race, age, mean intraocular pressure (IOP), baseline disease severity, and central corneal thickness (CCT). The relationship between the timing of DH and the rates of RNFL thinning also was investigated in eyes with a history of DH. Rates of global and local RNFL thinning. Previous DH was significantly associated with faster RNFL thinning rates globally (-0.39 μm/year faster, P= 0.010), in DH quadrants (-0.77 μm/year faster, P= 0.012), and non-DH quadrants (-0.49 μm/year faster, P= 0.038) after adjustment for race, mean IOP, baseline age, baseline standard automated perimetry mean deviation, and CCT. Higher IOP was also significantly associated with faster thinning rates globally (-0.07 μm/year faster per 1 mmHg higher, P= 0.047) and in DH quadrants (-0.10 μm/year faster per 1 mmHg higher, P= 0.044). In eyes with a history of DH, the time elapsed from the latest DH episode to the first OCT examination was not significantly associated with the rate of RNFL thinning. A history of DH is an independent risk factor for faster rates of RNFL thinning in non-DH quadrants and in DH quadrants; this risk is present even in eyes that exhibited DH several years earlier.