Serial Spectral-domain Optical Coherence Research Articles

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.

Rate of Retinal Nerve Fiber Layer Thinning in Glaucomatous Eyes with Optic Disc and Parapapillary Deep-Layer Microvasculature Loss.

Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself. To characterize open-angle glaucoma (OAG) eyes with optic nerve head (ONH) deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate. This study included 122 OAG eyes that underwent ≥5 serial spectral-domain optical coherence tomography (OCT) scans during a mean follow-up of 5.4 years. Swept-source OCT angiography (SS-OCTA) was used to evaluate MvD-P and MvD-D. Subjects were classified into three groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the three groups, and the associated factors were assessed by Cox proportional hazard analysis. RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (-0.24 vs. -0.65 vs. -1.20μm/year, P<0.001). Thinner central corneal thickness (hazard ratio [HR]=0.990, P=0.003), presence of disc hemorrhage (HR=1.802, P=0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P<0.001) were the factors associated with RNFL thinning. The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using SS-OCTA may be clinically relevant in monitoring glaucoma progression.

Optic Neuritis-Independent Retinal Atrophy in Neuromyelitis Optica Spectrum Disorder.

A limited number of studies have investigated the presence of ongoing disease activity independent of clinical relapses in neuromyelitis optica spectrum disorder (NMOSD), and data are conflicting. The objective of our study was to examine whether patients with aquaporin-4 (AQP4)-IgG seropositive NMOSD exhibit progressive retinal neuroaxonal loss, independently of optic neuritis (ON) attacks. In this single-center, longitudinal study, 32 AQP4-IgG+ NMOSD patients and 48 healthy controls (HC) were followed with serial spectral-domain optical coherence tomography and visual acuity (VA) assessments. NMOSD patients with ON less than 6 months before baseline were excluded, whereas data from patients with ON during follow-up were censored at the last visit before ON. VA worsening was defined as a decrease in monocular letter acuity ≥5 letters for high-contrast VA and ≥7 letters for low-contrast VA. Analyses were performed with mixed-effects linear regression models adjusted for age, sex, and race. The median follow-up duration was 4.2 years (interquartile range: 1.8-7.5). Relative to HC, NMOSD eyes had faster peripapillary retinal nerve fiber layer (pRNFL) (β = -0.25 µm/year faster, 95% confidence interval [CI]: -0.45 to -0.05, P = 0.014) and GCIPL thinning (β = -0.09 µm/year faster, 95% CI: -0.17 to 0, P = 0.05). This difference seemed to be driven by faster pRNFL and GCIPL thinning in NMOSD eyes without a history of ON compared with HC (GCIPL: β = -0.15 µm/year faster; P = 0.005; pRNFL: β = -0.43 µm/year faster, P < 0.001), whereas rates of pRNFL (β: -0.07 µm/year, P = 0.53) and GCIPL (β = -0.01 µm/year, P = 0.90) thinning did not differ between NMOSD-ON and HC eyes. Nine NMOSD eyes had VA worsening during follow-up. In this longitudinal study, we observed progressive pRNFL and GCIPL atrophy in AQP4-IgG+ NMOSD eyes unaffected by ON. These results support that subclinical involvement of the anterior visual pathway may occur in AQP4-IgG+ NMOSD.

Mitochondrial Transfer of the Mutant Human ND6T14484C Gene Causes Visual Loss and Optic Neuropathy.

PurposeTo evaluate the long-term effects of mitochondrial gene transfer of mutant human NADH ubiquinone oxidoreductase subunit VI (hND6T14484C) in the mouse eye.MethodsAdult mice were injected intravitreally with mitochondrial-targeted adeno-associated virus carrying either hND6T14484C or mitochondrial encoded mCherry. The delivery and expression of the interest gene were detected by polymerase chain reaction (PCR), quantitative PCR (qPCR), and immunostaining. The pathologic effects of the mutant gene in live mice were assessed with RNA-seq, serial spectral domain optical coherence tomography (SD-OCT), and pattern electroretinogram (PERG).ResultsDelivered hND6 was found 30-fold greater than endogenous mouse ND6 in microdissected retinal ganglion cells of hND6-injected mice. Compared to controls injected with mCherry, PERG amplitude of hND6 mice dropped significantly at 3 (P = 0.0023), 6 (P = 0.0058), and 15 (P = 0.031) months after injection. SD-OCT revealed swelling of the optic nerve head followed by the progressive retinal and optic nerve atrophy in hND6 mice. Furthermore, RNA-seq data showed a change in 381 transcripts’ expression in these mice compared to mCherry mice. Postmortem analysis showed hND6 mice had marked atrophy of the entire optic nerve, from the globe to the optic chiasm, and a significant loss of retinal ganglion cells compared to age-matched control mice (P = 1.7E-9).ConclusionsDelivered hND6T14484C induces visual loss and optic neuropathy in mice, the hallmarks of human Leber's hereditary optic neuropathy (LHON).Translational RelevanceResults from this study will help establish a novel strategy not only to generate an LHON animal model but also to provide a potential to treat this or any other mitochondrial diseases.

Vulnerability Zone of Glaucoma Progression in Combined Wide-field Optical Coherence Tomography Event-based Progression Analysis.

PurposeTo investigate the spatial characteristics and patterns of structural progression using the combined retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer event-based progression analysis feature provided by the Guided Progression Analysis (GPA) software of spectral-domain optical coherence tomography.MethodsIn this retrospective observational study, we evaluated 89 patients with open-angle glaucoma showing clinically confirmed structural progression within a minimum follow-up period of 3 years. For each eye, the RNFL and ganglion cell–inner plexiform layer GPA data were extracted from serial spectral-domain optical coherence tomography (HD-OCT 4000, Carl Zeiss Meditec, Inc., Dublin, CA) data from 2012 to 2017 (available in commercial report). A combined wide-field GPA map was merged using vascular landmark-guided superimposition of RNFL and ganglion cell–inner plexiform layer GPA event-based progression maps onto the RNFL image (resulting in the GPA PanoMaps: proposed in this study). The pattern of progressive structural changes was evaluated by comparing the baseline combined wide-field OCT deviation maps (PanoMap deviation maps: available in commercial report) and GPA PanoMaps at the time the first progression was detected and the GPA PanoMaps at the last follow-up. Spatial characteristics and patterns of glaucoma structural progression on GPA PanoMaps were evaluated.ResultsProgressive structural progression was detected most frequently at the macular vulnerability zone (MVZ), with the peripapillary and macular progression being well-correlated spatially. Compared with the baseline structural change on PanoMap, the progressive structural changes extended toward the fovea at both the peripapillary and macular areas. A spatial difference was observed between the areas where structural damage was frequently found on PanoMap (peripapillary inferoinferior sector and macular MVZ) and areas where progression was frequently found on GPA PanoMap (peripapillary and macular MVZ).ConclusionsThe patterns of progressive glaucomatous structural changes in both the peripapillary and macular areas were confirmed on the combined wide-field GPA map (GPA PanoMap). An analysis of the progression pattern using the GPA PanoMap facilitates the understanding of the spatial relation between the peripapillary and macular areas in glaucoma.

Age-Related Physiologic Thinning Rate of the Retinal Nerve Fiber Layer in Different Levels of Myopia.

Purpose To investigate the effect of refractive error on the physiologic thinning rate of the retinal nerve fiber layer (RNFL) in healthy eyes. Materials and Methods. This study analyzed 223 eyes of 141 healthy subjects followed for more than 5 years and underwent at least five serial spectral domain optical coherence tomography (SD-OCT) examinations. Longitudinal RNFL measurements were analyzed by linear mixed models incorporating follow-up duration, baseline RNFL thickness, spherical equivalent (SE), age, intraocular pressure, and visual field mean deviation. Thinning rates were classified according to SE into three groups: nonmyopic (NM; >0 D), mild-to-moderately myopic (MM; >–6 D and ≤0 D), and highly myopic (HM; ≤–6 D). Results The overall slopes of change in RNFL thickness over time in the NM, MM, and HM groups were −0.305 ± 0.128, −0.294 ± 0.068, and −0.208 ± 0.097 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 Conclusions Refractive error did not affect the physiologic thinning rate of RNFL when assessed by SD OCT.

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.

Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up.

PurposeTo longitudinally characterize structural retinal changes in achromatopsia (ACHM) over extended follow-up.MethodsFifty molecularly confirmed ACHM subjects underwent serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Foveal structure on SD-OCT was graded and compared for evidence of progression, and foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness were serially measured. FAF patterns were characterized and compared over time.ResultsMean SD-OCT follow-up was 61.6 months (age range at baseline, 6–52 years). Forty-five of the subjects had serial FAF (mean follow-up: 48.5 months). Only 6 (12%) of the subjects demonstrated qualitative change on serial foveal SD-OCT scans. Among the entire cohort, there was no statistically significant change over time in FTRT (P = 0.2459) or hyporeflective zone (HRZ) diameter (P = 0.3737). There was a small—but statistically significant—increase in ONL thickness (P = 0.0084). Three different FAF patterns were observed: centrally increased FAF (13/45), normal FAF (14/45), and well-demarcated reduced FAF (18/45), with the latter group displaying a small gradual increase in the area of reduced FAF of 0.055 mm2 over 43.4 months (P = 0.0011).ConclusionsThis longitudinal study of retinal structure in ACHM represents the largest cohort and longest follow-up period to date. Our findings support the presiding notion that ACHM is essentially a stationary condition regarding retinal structure, and any change over time is likely to be small, slow, and variable across patients. This may potentially afford a wider window for therapeutic intervention.

A Small Molecule TrkB Neurotrophin Receptor Partial Agonist as Possible Treatment for Experimental Nonarteritic Anterior Ischemic Optic Neuropathy

ABSTRACT Purpose Brain-derived neurotrophic factor (BDNF) and activation of its high affinity receptor tropomyosin kinase (Trk) B promote retinal ganglion cells (RGCs) survival following injury. In this study, we tested the effects of LM22A-4, a small molecule TrkB receptor-specific partial agonist, on RGC survival in vitro and in experimental nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in those older than 50 years. Methods We assessed drug effects on immunopanned, cultured RGCs and calculated RGC survival and assessed TrkB receptor activation by mitogen-activated protein (MAP) kinase translocation. To assess effects in vivo, we induced murine AION and treated the animals with one intravitreal injection and three-week systemic treatment. We measured drug effects using serial spectral-domain optical coherence tomography (OCT) and quantified retinal Brn3A+ RGC density three weeks after ischemia. Results In vitro, LM22A-4 significantly increased the survival of cultured RGCs at day 2 (95% CI control: 8.4–13.6; LM22A-4: 23.7–30.3; BDNF: 24.3–29.9; P ≤ 0.0001), similar to the effect of the endogenous TrkB receptor ligand BDNF. There was also significant nuclear and cytoplasmic translocation of MAP kinase (95% CI control: 0.9–6.8; LM22A-4: 38.8–84.4; BDNF: 64.0–93.0; P = 0.0002), a known downstream event of TrkB receptor activation. Following AION, LM22A-4 treatment led to significant preservation of the ganglion cell complex (95% CI: AION-PBS: 66.8–70.7%; AION-LM22A-4: 70.0–73.1; P = 0.03) and total retinal thickness (95% CI: AION-PBS: 185–196%; AION-LM22A-4: 195–203; P = 0.002) as measured by OCT compared with non-treated eyes. There was also significant rescue of the Brn3A+ RGC density on morphometric analysis of whole mount retinae (95% CI control: 2360–2629; AION-PBS: 1647–2008 cells/mm2; AION-LM22A-4: 1958–2216 cells/mm2; P = 0.02). Conclusions TrkB receptor partial agonist LM22A-4 promoted survival of cultured RGCs in vitro by TrkB receptor activation, and treatment in vivo led to increased survival of RGCs after optic nerve ischemia, providing support that LM22A-4 may be effective therapy to treat ischemic optic neuropathy. Abbreviations AION: anterior ischemic optic neuropathy, BDNF: Brain-derived neurotrophic factor, GCC: ganglion cell complex, MAP: mitogen-activated protein, OCT: spectral-domain optical coherence tomography, OD: right eye, ON: optic nerve, ONH: optic nerve head, OS: left eye, RGC: retinal ganglion cell; Trk: tropomyosin kinase

Epiretinal Proliferations Associated with Lamellar Macular Holes: Clinical and Surgical Implications

Objectives: To describe the prevalence of lamellar hole-associated epiretinal proliferation (LHEP) and to correlate this finding with lamellar macular hole (LMH) morphology and prognosis after a surgical or conservative approach. Methods: This is a retrospective multicenter case series comprising consecutive LMH patients followed for ≥6 months. Serial spectral-domain optical coherence tomographies were evaluated for the presence of epiretinal membrane (ERM) and LHEP, diameter of the LMH aperture, base, and floor thickness. Pars plana vitrectomy with ERM and internal limiting membrane peeling was performed in the surgical cases. Results: A total of 62 eyes from 57 consecutive patients were included. Mean follow-up time was 27.1 ± 19.8 months. LHEP was observed in 33 (53.2%) eyes. Patients with LMH and LHEP presented a larger external diameter (p = 0.001) and thinner floors (p = 0.018). Twenty-seven (81.8%) of the patients with LMH and LHEP presented a degenerative intraretinal cavitation, compared to 23.3% in the non-LHEP group (p = 0.001). No differences were observed in visual performance or closure rate between the 2 groups after surgery or in the subset of patients followed conservatively. Conclusions: LHEP was correlated with the anatomical conformation of the LMH, yielding thinner floors and larger external diameters. However, it did not correlate with the anatomical or functional results, both in the patients who underwent surgery and in those managed conservatively.

Utility of spectral domain optical coherence tomography in a case of choroidal metastasis to monitor response to treatment

Serial spectral domain optical coherence tomography (SD-OCT) images can be applied to monitor the effectiveness of systemic treatment in choroidal metastasis. Besides, it can be used as a guide to shifting to alternate therapy in nonresponding cases. SD-OCT was performed in a patient of primary adenocarcinoma of the lung with choroidal metastasis in the right eye. SD-OCT revealed neurosensory detachment overlying metastasis and involving macula. The patient was started on chemotherapy and external beam radiotherapy. After treatment completion, neurosensory detachment resolved completely with the regaining of normal foveal contour and improvement in visual acuity.

Vitrectomy with fibrovascular membrane delamination for proliferative diabetic retinopathy with or without preoperative Avastin.

To describe and compare 1. The changes in intraretinal microstructure using serial spectral domain optical coherence tomography (SD-OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes and 2. Intraoperative and postoperative complications in patients with proliferative diabetic retinopathy (PDR) who had preoperative Avastin (group A) or not (group B). This retrospective, interventional case series includes 113 eyes. Outcome measures included LogMAR distance best-corrected visual acuity (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM), intraoperative and postoperative complications. Pre-operative central macular thickness (CMT) was significantly correlated with the final post-operative LogMAR BCVA in group A. Both groups were also categorised into three sub-groups based on post-operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly and IS/OS integrity and ELM integrity postoperatively, were significantly and positively correlated with final BCVA in group A. Intraoperative complications such as iatrogenic tears and haemorrhage and postoperative such as vitreous haemorrhage and neovascular glaucoma were significantly less in group A compared to group B. Pre-operative Avastin reduces the risk of intraoperative and postoperative complications and results in better postoperative anatomic and functional outcomes in fibrovascular delamination surgery for patients with PDR.

Serial Spectral-Domain Optical Coherence Tomography Findings in Acute Retinal Pigment Epitheliitis and the Correlation to Visual Acuity

To evaluate the features of acute retinal pigment epitheliitis (ARPE) at onset and in the course of recovery by serial spectral-domain optical coherence tomography (SD OCT) and the correlation to visual acuity (VA). Retrospective cohort study. Consecutive patients with ARPE. A review of medical records was performed. Integrity of SD OCT retinal bands at onset and in the course of disease, time required to achieve each retinal band restoration, corresponding VA change, and final VA. Four patients were included. Initial SD OCT showed a dome-shaped hyper-reflective lesion at the photoreceptor outer segment layer disrupting the ellipsoid zone (EZ) and interdigitation zone (IZ) (100%). In the early phase, there was also upward displacement of the external limiting membrane (ELM) and mild transient thickening of the retinal pigment epithelium (RPE)/Bruch's complex (Bc). Acute retinal pigment epitheliitis resolved in a sequence of (1) a decrease in height of SD OCT hyper-reflective lesion and the upwardly displaced ELM returning to its normal position with irregularity; (2) complete disappearance of the hyper-reflective lesion; (3) restoration of ELM; (4) restoration of EZ; and (5) restoration of IZ. The average time to restore ELM, EZ, and IZ was 4.3±5.2, 7.3±7.2, and 12.5±12.4 weeks, respectively, and the corresponding logarithm of the minimum angles of resolution (logMAR) VAs were 0.24±0.23, 0.09±0.07, and 0.05±0.06, respectively. Visual acuity improved when IZ was restored. Early SD OCT revealed an inflammatory lesion in the photoreceptor outer segment layer displacing ELM. The RPE was involved only mildly and transiently. Recovery occurred in a sequence of ELM, EZ, and IZ restoration, and VA improved when the IZ was restored. These features suggested that the IZ (i.e., the contact between photoreceptors and RPE) is the primary site of inflammation in ARPE.

Changes in morphology and visual function over time in mouse models of retinal degeneration: an SD-OCT, histology, and electroretinography study.

To examine the long-term natural course of retinal degeneration in rd10 and rd12 mice using serial spectral-domain optical coherence tomography (SD-OCT), electroretinography/electroretinograms (ERGs), and histological analysis. Photoreceptor layer thickness and the ability to visualize photoreceptor ellipsoid zones were analyzed using SD-OCT images, and these images were compared with hematoxylin and eosin-stained sections and electron microscopy images. The a- and b-wave amplitudes of the ERGs were analyzed. In rd10 mice, the photoreceptor layer thickness rapidly decreased, and the photoreceptor ellipsoid zone was visible on SD-OCT images in 89 and 43 % of eyes of 21 and 33-day-old mice, respectively. In rd12 mice, the photoreceptor layer gradually thinned, and the ellipsoid zone remained visible in 92 % of eyes at 19 months. Electron microscopy revealed that photoreceptor degeneration had occurred on the inner side of the outer nuclear layer in 21-day-old rd10 and 7-month-old rd12 mice, possibly due to autophagy mechanisms. Scotopic ERGs of rd10 mice showed a diminished response at 21 days; at 33 days, no response was detectable. In rd12 mice, scotopic ERGs were undetectable at 28 days (stimulus intensity 3.0 cds/m(2)). Photopic ERGs were nearly undetectable in 28-day-old rd10 mice, but a small b-wave was still recordable in 13-month-old rd12 mice. Our results demonstrate that visual function deteriorated with photoreceptor degeneration within 1 month in rd10 mice. In rd12 mice, however, the process of visual function deterioration and photoreceptor degeneration was still in progress at 13 months of age.

Macular Ganglion Cell Layer Assessment to Detect Glaucomatous Central Visual Field Progression

PurposeTo investigate the use of ganglion cell inner plexiform layer (GC-IPL) thickness, as measured by spectral domain optical coherence tomography, to detect central visual field (VF) progression.MethodsThis study included 384 eyes from 384 patients (219 preperimetric and 165 perimetric glaucomatous eyes; average follow-up, 4.3 years). Photographic assessment of retinal nerve fiber layer (RNFL) and serial VF analysis were performed to detect glaucoma progression in the central (within 10°) area. Study inclusion required at least five serial spectral domain optical coherence tomography exams at different visits. The long-term test-retest variability of average GC-IPL thicknesses was calculated in 110 stable preperimetric glaucomatous eyes. The sensitivity and specificity of GC-IPL measurements for the detection of central VF progression were calculated in an event-based analysis using the calculated variability as a cut-off and were compared with those of central RNFL photographic assessment.ResultsThe intersession test-retest variability, defined as the 95% confidence interval, was 1.76 µm for average GC-IPL thickness. The sensitivity and specificity of the average GC-IPL thickness for detecting central VF progression were 60.7% and 78.9%, respectively. Among six sectors, the inferonasal GC-IPL sector showed the highest sensitivity (53.6%). The sensitivity of the ≥1 sector GC-IPL to detect central VF progression was significantly higher than that of central RNFL photographic progression (p = 0.013). Other GC-IPL parameters showed comparable sensitivity and specificity to detect central VF progression compared with RNFL photographic progression.ConclusionsSerial GC-IPL measurements show comparable performance in the detection of central glaucomatous VF progression to RNFL photographic assessment.

Spectral domain ocular coherence tomography findings pre- and post vitrectomy with fibrovascular membrane delamination for proliferative diabetic retinopathy.

PurposeTo describe the intraretinal microstructure using serial spectral domain optical coherence tomography (SD-OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR).MethodsThis retrospective, interventional case series includes 28 eyes. Outcome measures included LogMAR distance best-corrected visual acuity (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM).ResultsPre-operative central macular thickness (CMT) was significantly correlated with the final post-operative LogMAR BCVA (Pearson's coefficient r=0.89; P=0.001). The eyes were categorised into three groups based on post-operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly in group 0 (n=9) from 1.13±0.75 preoperatively to 0.34±0.21 (Student's t-test: P=0.06), in group 1 (n=10) the BCVA improved from 0.88±0.56 to 0.58±0.31 (Student's t-test: P=0.053) and in group 2 (n=9) the BCVA improved from 1.64±0.53 to 1.53±0.75 (Student's t-test: P=0.652).IS/OS integrity and ELM integrity at 3 months post operatively, were significantly and positively correlated with final BCVA (Pearson's coefficient: r=0.83, P<0.001 and r=0.72, P<0.001, respectively).ConclusionsPre-operative CMT and post-operative disruption of the IS/OS and ELM are useful prognostic indicators in fibrovascular delamination surgery for patients with PDR.

Lamina Cribrosa Reversal after Trabeculectomy and the Rate of Progressive Retinal Nerve Fiber Layer Thinning

To determine whether the reversal of lamina cribrosa (LC) displacement observed after trabeculectomy is associated with the rate of progressive retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG). Observational case series. Thirty-four patients with POAG who underwent trabeculectomy and were followed up for at least 2.5 years, during which the RNFL thickness was measured by serial spectral-domain (SD) optical coherence tomography (OCT). The participants underwent enhanced depth imaging scanning of the optic nerve using SD OCT before surgery (PREOP), at a 6-month postoperative follow-up (FU1), and at a subsequent follow-up that was performed at least 2.5 years postoperatively (FU2), and serial RNFL thickness was measured at least 5 times during the study period. Preoperative and postoperative LC depths (LCDs) as determined on 7 selected B-scan images from each eye were averaged to produce the mean LCD. The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements over time. Factors associated with the rate of OCT RNFL thinning. The intraocular pressure (IOP) decreased from 23.8±7.9 mmHg (mean±standard deviation) to 11.0±4.4 mmHg at FU1 (P<0.001) and subsequently increased to 13.1±5.2 mmHg at an overall follow-up of 3.5±0.8 years (P=0.003). The LCD was reduced from 589.90±148.32 to 508.57±136.28 μm at FU1 (P<0.001). A subsequent slight but nonsignificant increase in the LCD was noted at FU2 (516.48±145.87 μm; P=0.410). A faster rate of RNFL thinning was associated with a shorter follow-up period (P=0.032), higher IOP at PREOP (P=0.011) and FU2 (P=0.014), and a larger increase in LCD from FU1 to FU2 (P<0.001). The changes in LCD between PREOP and FU1 and between PREOP and FU2 were not associated with the rate of RNFL thinning. Eyes with sustained LCD reduction over a long period had a slow rate of progressive RNFL thinning after trabeculectomy. A large LCD reduction in the early postoperative period was not associated with the long-term rate of progression if it was not maintained during subsequent follow-up.

Influence of Lamina Cribrosa Thickness and Depth on the Rate of Progressive Retinal Nerve Fiber Layer Thinning

To determine whether lamina cribrosa (LC) depth (LCD) and LC thickness (LCT) are associated with a faster rate of progressive retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG). Prospective, observational study. One hundred ten eyes diagnosed with POAG (n = 110 patients) in which RNFL thickness had been measured by serial spectral-domain (SD) optical coherence tomography (OCT) for at least 2.5 years. The participants underwent enhanced depth imaging volume scanning of the optic nerve, and circumpapillary RNFL thickness measurements were obtained using SD OCT. The participants were followed up regularly with serial RNFL thickness measurements at 6-month or longer intervals. Lamina cribrosa depth was measured at 7 equidistant planes and LCT was measured at 3 locations (superior midperipheral, midhorizontal, and inferior midperipheral). The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements over time. Factors associated with the rate of OCT RNFL thinning. A faster rate of RNFL thinning was associated with disc hemorrhage during follow-up (P < 0.001), wider β-zone parapapillary atrophy with Bruch's membrane (P = 0.037), larger global RNFL thickness (P = 0.026), larger LCD (P < 0.001), and smaller LCT (P = 0.002). The association between LCD and the rate of RNFL thinning was explained better using a fractional polynomial model (R(2) = 0.223) than a linear model (R(2) = 0.134; P = 0.010). Davies' test revealed a statistically significant breakpoint for LCD (489.7 μm), above which a faster rate of global RNFL thinning was associated with a larger LCD. A thinner LC and a larger LC displacement had a significant influence on the rate of progressive RNFL thinning.

Management of choroidal neovascularisation in late onset retinal degeneration

AbstractPurpose Late onset retinal degeneration is a hereditary condition characterized by progressive difficulty in dark adaptation and risk of choroidal neovascularisation. This in turn leads to a marked decline in visual acuity. We describe our experience treating a patient with a positive family history of late onset retinal degeneration who developed subfoveal choroidal neovascularisation.Methods Case report. A 57 year old Caucasian lady with a positive family history of late onset retinal degeneration and progressive decline in dark adaptation presented to us with a 1‐week history of blurring of vision. Fundus fluorescein and indocyanine green angiography revealed a subfoveal classic neovascular membrane.Results Our patient was initially treated with intra‐vitreal Ranibizumab and clinical activity of neovascularisation was monitored with serial spectral domain optical coherence tomography and visual acuity. Serial scans revealed recurrence of activity within a month of intra‐vitreal Ranibizumab. With the advent of intra‐vitreal Aflibercept, we offered our patient a change in treatment regime. Treatment with Aflibercept has thus far demonstrated a stabilization of disease activity on spectral domain optical coherence tomography and visual acuity for at least 8 weeks.Conclusion Whilst Ranibizumab and Aflibercept remain off‐label for the treatment of late onset retinal degeneration, this suggests that Aflibercept is possibly more efficacious in the management of choroidal neovascular membranes in late onset retinal degeneration.

Metastatic carcinoma to the vitreous: an optical coherence tomography and ultrawide field imaging study

Metastatic carcinoma to the vitreous: an optical coherence tomography and ultrawide field imaging study