GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION OF DIFFERENT DRUSEN SUBTYPES.

PURPOSE: We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration. METHODS: We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups. RESULTS: We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001). CONCLUSION: The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

BACILLARY LAYER DETACHMENT BECAUSE OF MACULAR NEOVASCULARIZATION.

PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

Beyond Performance Metrics: Automatic Deep Learning Retinal OCT Analysis Reproduces Clinical Trial Outcome.

PURPOSE: To validate the efficacy of a fully automatic, deep learning-based segmentation algorithm beyond conventional performance metrics by measuring the primary outcome of a clinical trial for macular telangiectasia type 2 (MacTel2). DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: A total of 92 eyes from 62 participants with MacTel2 from a phase 2 clinical trial (NCT01949324) randomized to 1 of 2 treatment groups METHODS: The ellipsoid zone (EZ) defect areas were measured on spectral domain OCT images of each eye at 2 time points (baseline and month 24) by a fully automatic, deep learning-based segmentation algorithm. The change in EZ defect area from baseline to month 24 was calculated and analyzed according to the clinical trial protocol. MAIN OUTCOME MEASURE: Difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups. RESULTS: The difference in the change in EZ defect area from baseline to month 24 between the 2 treatment groups measured by the fully automatic segmentation algorithm was 0.072±0.035 mm2 (P = 0.021). This was comparable to the outcome of the clinical trial using semiautomatic measurements by expert readers, 0.065±0.033 mm2 (P = 0.025). CONCLUSIONS: The fully automatic segmentation algorithm was as accurate as semiautomatic expert segmentation to assess EZ defect areas and was able to reliably reproduce the statistically significant primary outcome measure of the clinical trial. This approach, to validate the performance of an automatic segmentation algorithm on the primary clinical trial end point, provides a robust gauge of its clinical applicability.

ATTENUATION OUTER RETINAL BANDS ON OPTICAL COHERENCE TOMOGRAPHY FOLLOWING MACULAR EDEMA: A Possible Manifestation of Photoreceptor Misalignment.

PURPOSE: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema. METHODS: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics. RESULTS: Included patients comprised two women and seven men (age range, 19-76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands. CONCLUSION: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles-Crawford effect to disambiguate missing from misaligned cones.

Structural changes of macular inner retinal layers in early normal-tension and high-tension glaucoma by spectral-domain optical coherence tomography.

PURPOSE: Assessment of the diagnostic ability of segmented macular inner retinal layer thickness and peripapillary retinal nerve fiber layer (pRNFL) measured by spectral-domain optical coherence tomography (SD-OCT) in patients with normal-tension (NT) and high-tension (HT) perimetric and preperimetric glaucoma. METHODS: The 212 participants included 45 healthy subjects, 55 patients with ocular hypertension, 56 patients with preperimetric glaucoma, and 56 patients with perimetric glaucoma. The preperimetric and perimetric groups were further subdivided into NT and HT groups. Sectoral and global thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), ganglion cell complex (mGCC), and pRNFL were measured using SD-OCT (Spectralis, Heidelberg Engineering, Germany). Diagnostic performance was ascertained by sectoral and global comparison of the sensitivities at specificity ≥ 95%. RESULTS: For all layers, the largest thickness decrease was reported in the HT perimetric group. In all groups, the sensitivities of mGCL showed a comparable diagnostic value to pRNFL in order to distinguish between healthy subjects and glaucoma patients. In the perimetric group, mGCL (85.7%) exhibited higher sensitivities than mRNFL (78.6%) and mGCC (78.6%). Both mRNFL and pRNFL demonstrated equal diagnostic performance in the HT perimetric group (88.5 and 96.2%), in the NT groups, mRNFL was inferior to all other layers. CONCLUSION: The sensitivities of mGCL and mRNFL were comparable to the sensitivities of pRNFL. In clinical application, mGCL and mRNFL, with a focus on the temporal and inferior sectors, may provide a convincing supplementation to pRNFL. CLINICAL TRIAL REGISTRATION: Erlangen Glaucoma Registry www.clinicaltrials.gov ID: NCT00494923.

CORRELATION BETWEEN INNER-RETINAL CHANGES AND OUTER-RETINAL DAMAGE IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE.

PURPOSE: To investigate correlations between the inner-retinal irregularity index and interdigitation zone (IZ) defects preidiopathic and postidiopathic epiretinal membrane (ERM) surgery. METHODS: The authors retrospectively assessed ophthalmic parameters in 89 eyes of 89 patients with ERM. They divided patients into the no-IZ defect (51, 57%) and IZ defect (38, 43%) groups. The IZ defect group was subdivided into recovered (22, 58%) and remaining IZ defect (16, 42%) subgroups, according to IZ recovery status at final examination. The inner-retinal irregularity index of each group was measured before and 1-, 3-, and 6-month postsurgery. RESULTS: Clinical characteristics were similar in both groups. The IZ defect group had a statistically significant higher inner-retinal irregularity index than the no-IZ defect group before (P = 0.023), but not after ERM surgery. The inner-retinal irregularity index of the recovered and remaining IZ defect subgroups was similar before surgery, but differed markedly 6 months after surgery (P = 0.048). Changes in the inner-retinal irregularity index quantitatively correlated with IZ defect size before and after ERM surgery (P < 0.001). CONCLUSION: The inner-retinal irregularity index differed significantly according to the IZ status and also correlated with the IZ defect before and after ERM surgery. The inner-retinal irregularity index may reflect the outer-retinal damage in ERM.

BIOMARKERS OF NEOVASCULAR ACTIVITY IN AGE-RELATED MACULAR DEGENERATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the qualitative and quantitative features of choroidal neovascular (NV) membranes in age-related macular degeneration using optical coherence tomography angiography in patients with active and quiescent NV lesions before and after treatment with anti-vascular endothelial growth factor. METHODS: Macular optical coherence tomography angiography images were obtained using RTVue XR Avanti with AngioVue. Morphologic features and quantitative measurements of the NV lesion were analyzed using en face projection images. The NV lesion was subdivided into inner segment and outer fringe for further fractal dimension analysis. RESULTS: In a series of 31 eyes, 11 eyes with active NV lesions at baseline and after consecutive follow-up after treatment with anti-vascular endothelial growth factor therapy and 20 eyes with quiescent NV lesions were included in this study. Morphologically, all the quiescent NV lesions versus 63.6% of the active NV lesions demonstrated a prominent central vessel and active leasions demonstrated a greater rate of small vessels branching (82%) and peripheral arcades (82%) than quiescent lesions (30% and 40% respectively) and this was statistically significant. The lesion area and vessel density was not statistically significantly different after treatment or versus quiescent lesions although the latter lesions were reduced in area. Lesion pattern complexity measured by the fractal dimension was statistically significantly lower in the inner part of the lesion after treatment and statistically significantly lower in the total lesion of the quiescent NV compared with the active NV. CONCLUSION: Optical coherence tomography angiography is a new, noninvasive imaging modality that can be used to perform qualitative and quantitative analyses of NV lesions. In the future, OCT angiography may provide biomarkers of activity and guide the evaluation and treatment and monitoring of neovascularization in age-related macular degeneration.

Reduction of foveal bulges and other anatomical changes in fellow eyes of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes.

PURPOSE: To compare the foveal characteristics in fellow eyes (FE) of patients with unilateral idiopathic macular hole without vitreomacular pathologic changes with eyes of healthy controls. METHODS: Forty-seven FE and 52 eyes of 52 age- and sex-matched healthy controls were studied. Quantitative assessment of the dome-shaped appearance of the hyperreflective lines that represent external limiting membrane (ELM_bulge) and inner outer segment junctions (IS/OS_bulge) were made by optical coherence tomography (OCT) images. Inner retinal complex thickness (IRCT) was quantitatively assessed at 1000 and 2000 µm of the foveal center in nasal and temporal quadrants. Presence of alterations in the inner retinal outer layers and central foveal thickness (CFT) were also analyzed. RESULTS: Significantly lower ELM_bulge (p < 0.0001; Mann-Whitney test) and IS/OS_bulge (p < 0.001; student t test) and higher cases with COST alterations, expressed as a diffuse line (p < 0.006; Chi2 test) were found in FE than control eyes. IRCT were significantly reduced in FE at all the studied locations when comparing to control eyes (p < 0.05; student t test), maintaining anatomical proportionality among locations. CONCLUSION: FE without pathologic vitreomacular interactions seems to present some central cone alterations that may be related to other causes than vitreomacular traction.

Inner retinal layer change in glaucoma patients receiving anti-VEGF for neovascular age related macular degeneration.

PURPOSE: The purpose was to evaluate the effects of long-term anti-VEGF treatment on the retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (RGCL) thickness for patients with neovascular AMD and glaucoma. METHODS: Medical records of respective patients who had received more than 15 anti-VEGF injections were reviewed. Initial and latest SD-OCT macular scans were segmented and changes of the RNFL and RGCL thickness at the four outer ETDRS quadrants were evaluated. Secondary outcome measures included changes of visual field parameters seen in automated perimetry. RESULTS: Sixteen patients were included (mean age 78 ± 6 years). The mean total number of anti-VEGF injections was 39 ± 16. The mean treatment duration was 6.1 ± 2.1 years. The mean IOP decreased from 18 ± 5 mmHg at baseline to 15 ± 5 mmHg at the last visit (p = 0.026). The mean RNFL thickness volume of the outer ETDRS quadrants (0.98 ± 0.18 mm3 to 0.97 ± 0.18 mm3 p = 0.61) and its average thickness (37.9 ± 7.3 µm to 37.2 ± 7.4 µm, p = 0.6) did not significantly change. However, the average RGCL thickness decreased significantly from 0.86 ± 0.12 mm3 to 0.79 ± 0.11 mm3 (p = 0.01), and from 27.7 ± 4.2 to 25.9 ± 3.7 µm (p = 0.01). Number of injections correlated with the RGCL change (r2 = 0.36, p = 0.01). The mean sensitivity, mean defect and absolute scotomata did not significantly change with p-values of 0.28, 0.21 and 0.07, respectively. CONCLUSION: Patients under long term treatment with anti-VEGF and concurrent glaucoma show significant decrease in macular RGLC volume. However, this decrease is comparable to reported RGCL decrease in patients under anti-VEGF treatment without underlying glaucoma and suggests that glaucoma patients may not be at a higher risk for losing macular RNFL and RGCL, at least if adequate control of intraocular pressure is maintained.

PHOTORECEPTOR INNER SEGMENT MORPHOLOGY IN BEST VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors. METHODS: Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period. RESULTS: The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed. CONCLUSION: Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD.

MACULAR MICROSTRUCTURAL FEATURES IN CHILDREN WITH TILTED DISK SYNDROME EVALUATED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To assess macular microstructure in eyes with tilted disk syndrome (TDS) and determine the relationship between TDS foveal morphology and visual function. METHODS: Twenty-six TDS eyes from 19 children (aged 5∼15 years) with a spherical equivalent refraction (SER) of -3.1 ± 1.3 diopter (D) and 28 control eyes from 14 children (aged 7∼12 years) with a SER of -3.0 ± 0.7 D were recruited. Horizontal and vertical optical coherence tomography scans through the fovea produced images that were segmented into eight intraretinal layers. Thicknesses of the total retina and each layer were measured at the foveal center and 12 other macular locations: 500 µm, 1,000 µm, and 1,500 µm along the horizontal and vertical meridians. The relationships between TDS best correct visual acuity (BCVA) and the presence of photoreceptor inner/outer segment (IS/OS) junction line, IS/OS foveal bulge, and cone outer segment tip (COST) line were evaluated. RESULTS: The thickness of TDS central fovea, 218.94 ± 22.20 µm, was not significantly different from controls. The total retinal thickness in TDS eyes was thinner than controls at all peripheral locations (P < 0.05) except at 500 µm and 1,000 µm superiorly, and 1,500 µm temporally. Tilted disk syndrome intraretinal layer thicknesses in the nasal and inferior regions varied significantly from controls (P < 0.05). Only 80.7% and 23.1% of TDS eyes had a normal foveal bulge and continuous COST line, respectively, compared with 100% and 96.4% of controls. The BCVA of TDS eyes was similar whether or not the foveal bulge or COST line was abnormal. CONCLUSION: Differences in intraretinal layer thickness may be correlated with defective vision.

INCREASED SERUM LEVELS OF UREA AND CREATININE ARE SURROGATE MARKERS FOR DISRUPTION OF RETINAL PHOTORECEPTOR EXTERNAL LIMITING MEMBRANE AND INNER SEGMENT ELLIPSOID ZONE IN TYPE 2 DIABETES MELLITUS.

PURPOSE: To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time. METHODS: One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically. RESULTS: Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (γ = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001). CONCLUSION: Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.

Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells.

Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d-/- retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx.

Developing Stage-dependent Retinal Toxicity Induced by l-glutamate in Neonatal Rats.

The neurotransmitter glutamate causes excitotoxicity in the human retina. In neonatal rats, the degree of glutamate-induced retinal damage depends on age at administration. To elucidate the sensitivity to glutamate on various developing stage of retina, we investigated glutamate-induced retinal damage and glutamate target cells on each postnatal day (PND). Newborn rats received a single subcutaneous administration of l-glutamate on PNDs 1 to 14. Retinal cell apoptosis characterized as pyknotic and terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling-positive nuclei was analyzed at 6 hr after treatment, and sequential morphological features of retina were evaluated on PND 21. The inner retina on PND 21 exhibited thinning in rats treated after PND 2. The thinning was most severe in rats treated on PND 8 and the number of apoptotic cells also peaked. No thinning was observed in rats treated on PND 14. In the inner nuclear layer, glutamate target cells were mainly amacrine cells; additionally, bipolar cells and horizontal cells were damaged on PND 8. These retinal changes were more severe in central retina than those in peripheral retina on PND 8. Our findings indicate the morphological consequences of glutamate-induced retinal excitotoxicity and glutamate target cells on each PND and reveal that glutamate-induced retinal damage depends on developing stage.

Correlation between visual acuity changes and optical coherence tomography morphological findings in idiopathic epiretinal membranes.

PURPOSE: To analyze the influence of spectral-domain optical coherence tomography (SD-OCT) features on visual acuity changes in patients with idiopathic epiretinal membranes (ERMs). METHODS: Seventy-nine eyes of 71 patients were included in this study. SD-OCT was performed for all patients; data were collected upon ERM diagnosis and at the final visit. The patients were divided into subgroups based on their SD-OCT features. The initial best corrected visual acuity (BCVA) and changes in BCVA for each subgroup were compared. A multivariate analysis was performed to assess the factors associated with changes in BCVA. RESULTS: During a mean follow-up period of 20.78 months, the mean change in logMAR visual acuity was 0.052 ± 0.089. Eyes with inner segment/outer segment (IS/OS) junction disruption and cystoid macular edema (CME) had a significantly lower mean initial BCVA than those without disruption and CME (P = 0.036 and P = 0.012, respectively). However, only eyes with CME had significant changes in BCVA (P = .034). Multivariate analysis revealed the presence of CME as the only factor that had a significant correlation with VA changes. CONCLUSIONS: In patients with idiopathic ERMs, the presence of CME and IS/OS disruption detected by OCT correlated with a poorer initial BCVA. Most patients' visual acuity remained stable during follow-up. The presence of CME with OCT represented a predictor of the progression of visual acuity. These results may provide valuable clinical information regarding the management of patients with idiopathic ERMs. We demonstrated that the presence of CME and IS/OS disruption detected with OCT correlated with a poorer BCVA in idiopathic ERMs. The visual acuity of most patients was stable during the follow-up period. The presence of CME in OCT represented a predictor of vision deterioration for patients with idiopathic ERMs.

New Developments in Murine Imaging for Assessing Photoreceptor Degeneration In Vivo.

Optical Coherence Tomography (OCT) is a powerful clinical tool that measures near infrared light backscattered from the eye and other tissues. OCT is used for assessing changes in retinal structure, including layer thicknesses, detachments and the presence of drusen in patient populations. Our custom-built OCT system for the mouse eye quantitatively images all layers of the neural retinal, the RPE, Bruchs' membrane and the choroid. Longitudinal assessment of the same retinal region reveals that the relative intensities of retinal layers are highly stable in healthy tissue, but show progressive increases in intensity in a model of retinal degeneration. The observed changes in OCT signal have been correlated with ultrastructural disruptions that were most dramatic in the inner segments and nuclei of the rods. These early changes in photoreceptor structure coincided with activation of retinal microglia, which migrated vertically from the inner to the outer retina to phagocytose photoreceptor cell bodies (Levine et al., Vis Res 102:71-79, 2014). We conclude that quantitative analysis of OCT light scattering signals may be a useful tool for early detection and subcellular localization of cell stress prior to cell death, and for assessing the progression of degenerative disease over time. Future efforts to develop sensitive approaches for monitoring microglial dynamics in vivo may likewise elucidate earlier signs of cellular stress during retinal degeneration.

Nitric Oxide Synthase Activation as a Trigger of N-methyl-N-nitrosourea-Induced Photoreceptor Cell Death.

Retinal degeneration (RD) such as retinitis pigmentosa and age-related macular degeneration are major causes of blindness in adulthood. As one of the model for RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used because of its selective photoreceptor cell death. It has been reported that MNU increases intracellular calcium ions in the retina and induces photoreceptor cell death. Although calcium ion influx triggers the neuronal nitric oxide synthase (nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not been reported yet. In this study, we investigated the contribution of nNOS on photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS activation at 3 day after treatment. Then, we evaluated the effect of nNOS specific inhibitor, ethyl[4-(trifluoromethyl) phenyl]carbamimidothioate (ETPI) on the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the MNU-induced cell death in the ONL. These data indicate that nNOS is a key molecule for pathogenesis of MNU-induced photoreceptor cell death.

Inner and outer central retinal findings after surgery for rhegmatogenous retinal detachment using different spectral-domain optical coherence tomography devices.

PURPOSE: The aim of the study was to analyse macular changes after rhegmatogenous retinal detachment (RRD) repair using spectral-domain optical coherence tomography (SD-OCT). METHODS: Forty eyes with macula-on and 27 eyes with macula-off RRD underwent scleral buckling or vitrectomy and were postoperatively imaged using 2 SD-OCT devices (Cirrus® HD-OCT, RTVue-100®). Measurement of total and inner macular thickness consisting of ganglion cell layer + inner plexiform layer (GCL-IPL) using Cirrus or retinal nerve fibre layer + ganglion cell layer + inner plexiform layer (RNFL-GCL-IPL) using RTVue was performed. Results of inner macular thickness were compared with image results of 40 healthy controls. Qualitative analysis of inner and outer retinal layers was additionally assessed. RESULTS: Measurement of overall retinal thickness within the 9 ETDRS sectors was highly correlated between both OCTs (Pearson's r, range 0.88-0.99; p < 0.001). Correlation of RNFL-GCL-IPL complex between OCTs was excellent in both surgery groups (Pearson's r, range 0.73-0.88; p < 0.001) and normal controls (Pearson's r, range 0.79-0.90; p < 0.001). The RNFL-GCL-IPL complex was thicker in both surgery groups compared to normal controls using Cirrus. Outer retinal findings of macula-off patients were seen in four eyes (14.8 %). Visual acuity (VA) significantly improved in both groups independent of preoperative VA or duration of symptoms. CONCLUSION: Agreement between both OCTs was excellent for overall and inner retinal thickness, although RTVue measured a thicker RNFL-GCL-IPL complex. Thinning of inner retinal layers as a potential cause of poor VA was rarely detected, possibly due to tractional changes at the vitreomacular interface. VA improved even in patients with macula-involving RRD.

Role of ganglion cell complex in visual recovery following surgical internal limiting membrane peeling.

PURPOSE: To investigate the Ganglion Cell Complex (GCC) thickness change and visual recovery correlation after surgery for an idiopathic epiretinal membrane (ERM). METHODS: In this prospective, observational, case control study 30 eyes underwent vitrectomy for idiopathic ERM. We analysed best-corrected visual acuity (BCVA), mean macular thickness and mean GCC thickness one day before surgery, seven days and six months after surgery. Internal segment/outer segment junction, external limiting membrane, cone outer segment tips defects and intraretinalfluid were also investigated throughout the follow-up. RESULTS: Baseline GCC thickness was higher in patients with ERM (130 ± 13 µm) compared with healthy eyes (94 ± 5 µm; p < 0.0001). GCC thickness decreased after surgery to 89 ± 11 µm (p < 0.0001), reaching a value similar to controls (p = 0.12). Preoperative macular thickness was 318 ± 32 µm and decreased to 281 ± 18 µm (p < 0.0001), remaining significantly higher than controls (260 ± 8 µm; p < 0.0001). The GCC proportion of the whole macular thickness was also reduced six months after surgery (p < 0.0001). Post-operative BCVA gain showed direct correlation with GCC reduction (R = 0.67, p < 0.0001), but did not correlate with the mean macular thickness reduction (R < 0.01, p = 0.97). CONCLUSIONS: Ganglion cell complex thickness is higher in eyes with idiopathic ERM, and after surgery turns back to similar values of healthy eyes. Post-operative GCC reduction is proportionally higher than thinning of the whole retina, and this reduction is correlated with visual restoration.

Correlation between foveal interdigitation zone band defect and visual acuity after surgery for macular pseudohole.

PURPOSE: To determine the correlation between the integrity of the foveal microstructures and the best-corrected visual acuity (BCVA) after pars plana vitrectomy for a macular pseudohole. METHODS: Thirty-one eyes of 31 patients with a macular pseudohole underwent vitrectomy with internal limiting membrane removal. The foveal area was examined by spectral domain optical coherence tomography preoperatively and postoperatively. The correlations between the BCVA and the lengths of the photoreceptor interdigitation zone (IZ), the ellipsoid zone, and the external limiting membrane band defects, and central foveal thickness were determined. RESULTS: The BCVA improved significantly and the length of the IZ band defect decreased significantly after the surgery. Simple linear regression analyses showed that the BCVA was significantly correlated with the length of the IZ band defect preoperatively and also at 1 to 12 months postoperatively (P < 0.001 for all). The BCVA was not significantly correlated with the length of the ellipsoid zone, external limiting membrane band defect, and the central foveal thickness. CONCLUSION: The significant correlation between the length of the foveal IZ band defect and the BCVA preoperatively and postoperatively indicates that the foveal IZ band is related to the visual recovery in patients with macular pseudohole.