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.

Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses.

Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2-3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD.

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.

Alterations of retinal thickness measured by optical coherence tomography correlate with neurophysiological measures in diabetic polyneuropathy.

AIMS/INTRODUCTION: Diabetic polyneuropathy (DPN) and diabetic retinopathy (DR) are traditionally regarded as microvascular complications. However, these complications may share similar neurodegenerative pathologies. Here we evaluate the correlations in the severity of DPN and changes in the thickness of neuroretinal layers to elucidate whether these complications exist at similar stages of progression. MATERIALS AND METHODS: A total of 43 patients with type 2 diabetes underwent a nerve conduction study (NCS), a macular optical coherence tomography, and a carotid artery ultrasound scan. Diabetic polyneuropathy was classified according to Baba's classification using NCS. The retina was automatically segmented into four layers; ganglion cell complex (GCC), inner nuclear layer/outer plexiform layer (INL/OPL), outer nuclear layer/photoreceptor inner and outer segments, and retinal pigment epithelium (RPE). The thickness of each retinal layer was separately analyzed for the fovea and the parafovea. RESULTS: Fourteen patients were classified as having moderate to severe diabetic polyneuropathy. The thicknesses of the foveal and parafoveal INL/OPL increased in patients with diabetic polyneuropathy compared with patients without. The thickness of the parafoveal retinal pigment epithelium decreased in patients with diabetic polyneuropathy. The thinning of parafoveal ganglion cell complex and foveal and parafoveal retinal pigment epithelium were positively correlated with deterioration of nerve functions in the nerve conduction study, but the thickening of INL/OPL was positively correlated with the nerve function deterioration. The thinning of parafoveal ganglion cell complex and foveal retinal pigment epithelium were positively correlated with the thickening of the carotid intima-media. CONCLUSIONS: Depending on the progression of diabetic polyneuropathy, the ganglion cell complex and retinal pigment epithelium became thinner and the INL/OPL became thicker. These retinal changes might be noteworthy for pathological investigations and for the assessment of diabetic polyneuropathy and diabetic retinopathy.

Outer retinal involvement in N-methyl-D-aspartate-induced inner retinal injury in rabbits assessed by optical coherence tomography.

This study was aimed to investigate morphological alteration of the retina with N-methyl-D-aspartate (NMDA)-induced injury in rabbits by optical coherence tomography (OCT). The right and left eyes of a total of 12 rabbits received single-intravitreal injection of vehicle and NMDA, respectively. Four out of the 12 animals underwent OCT and quantification of plasma microRNA repeatedly (4, 48, and 168 hr after dosing), followed by ocular histopathology at the end of the study. Ocular histopathology was also conducted in the eyes collected 4 or 48 hr after dosing from 4 animals at each time period. OCT revealed hyper-reflective ganglion cell complex and thickened inner retina in NMDA-treated eyes 4 hr after dosing; the inner retina shifted to thinning at later time points. The eyes given NMDA also exhibited greater thickness of the outer retina, which contains photoreceptors, after treatment, and thickened and obscured ellipsoid zone 168 hr after dosing. The plasma levels of miR-182 and miR-183, which are known to be highly expressed in photoreceptors, were higher 4 hr after dosing than pre-dosing values. Histopathologically, NMDA-induced inner retinal damage was confirmed: single-cell necrosis was observed in the ganglion cell layer and the inner nuclear layer 4 hr after dosing, the incidence of which decreased thereafter. At 168 hr after dosing, reduced number of ganglion cells was noted. No change was histopathologically observed in the outer retina. In conclusion, our results suggest involvement of photoreceptors in NMDA-induced inner retinal injury. Additionally, OCT revealed acute inner retinal findings suggestive of temporary edema.

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.

Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS.

OBJECTIVE: To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. METHODS: In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months RESULTS: pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 µm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 µm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R2 0.36, p = 0.001). CONCLUSIONS: INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice.

Ellipsoid Zone Change According to Glaucoma Stage Advancement.

PURPOSE: To compare retinal photoreceptor ellipsoid zone (EZ) intensity between normal eyes and those with different stages of glaucoma. DESIGN: Retrospective cross-sectional study. METHODS: The study included 37 normal, 38 preperimetric glaucoma, 39 mild-to-moderate glaucoma (visual field [VF] mean deviation [MD]: -7.7 ± 2.0 dB), and 36 severe glaucoma eyes (VF MD: -17.8 ± 3.2 dB). The subjects underwent high-resolution horizontal and vertical line scans through the fovea by spectral-domain optical coherence tomography (SD-OCT). Image processing software was employed to quantify the intensity of the first and second hyperreflective bands corresponding with the external limiting membrane (ELM) and EZ. In order to account for the brightness variation among scans, the relative EZ intensity as the ratio of the second to first reflective band (EZ/ELM) was determined. RESULTS: The relative EZ intensity in severe glaucoma eyes was significantly lower than in mild-to-moderate glaucoma eyes (2.46 ± 0.38 vs 3.15 ± 0.43, P < .001); also, it was lower in mild-to-moderate than in preperimetric glaucoma eyes (3.15 ± 0.43 vs 3.86 ± 0.44, P < .001). However, the comparison between preperimetric glaucoma and normal eyes showed no significant difference (3.86 ± 0.44 vs 4.06 ± 0.40, P = .751). In 75 glaucomatous eyes with VF defect, there was a significant correlation between relative EZ intensity and VF MD (r = 0.83 and P < .001). CONCLUSIONS: According to SD-OCT, relative EZ intensity reduction occurs in the mild-to-moderate and severe glaucoma stages. These findings suggest, at least provisionally, that in the course of glaucoma progression, mitochondrial changes in the inner segments of photoreceptors occur. Further investigation is warranted to evaluate the potential clinical significance of EZ intensity reduction in glaucoma.

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.

The aging rat retina: from function to anatomy.

In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 days-22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases.

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.

Evaluation of Ganglion Cell-Inner Plexiform Layer Thinning in Eyes With Optic Disc Hemorrhage: A Trend-Based Progression Analysis.

Purpose: To evaluate the rate of change in ganglion cell-inner plexiform layer (GCIPL) thickness measured by optical coherence tomography (OCT) using a trend-based approach in early-stage glaucomatous eyes with disc hemorrhage (DH) and to compare the GCIPL thinning rate with that in glaucomatous eyes without DH. Methods: This prospective observational study included 46 patients with early-stage open-angle glaucoma and DH who underwent serial spectral-domain OCT measurements for at least 30 months. The GCIPL thinning rate was determined in the global, superior, or inferior hemiretinas and in six macular sectors by linear regression and was compared between glaucomatous eyes with DH and fellow glaucomatous eyes without DH and between glaucomatous eyes with DH and non-DH glaucomatous control eyes. Results: The GCIPL thinning rate (mean ± standard deviation) was significantly more rapid in glaucomatous eyes with DH than in fellow eyes without DH in the inferior hemiretina (-1.07 ± 0.75 vs. -0.44 ± 0.54 µm/y, P = 0.001), inferotemporal sector (-1.13 ± 1.00 vs. -0.61 ± 0.66 µm/y, P = 0.028), and inferior sector (-1.33 ± 0.79 vs. -0.42 ± 0.78 µm/y, P < 0.001). The GCIPL thinning rate was significantly more rapid in glaucomatous eyes with DH than in glaucomatous controls without DH in the global area (-0.78 ± 0.85 vs. -0.32 ± 0.48 µm/y, P = 0.002), the inferior hemiretina (-1.00 ± 0.94 vs. -0.37 ± 0.67 µm/y, P < 0.001), and the inferotemporal sector (-1.31 ± 1.07 vs. -0.34 ± 0.75 µm/y, P < 0.001). Conclusions: The GCIPL thinning rate on OCT was significantly more rapid in glaucomatous eyes with DH than in fellow glaucomatous eyes without DH or glaucomatous control eyes without DH. DH could be associated with progression of glaucoma in terms of GCIPL thinning.

Parafoveal Photoreceptor Abnormalities in Asymptomatic Patients With RP1L1 Mutations in Families With Occult Macular Dystrophy.

Purpose: To report the clinical characteristics of asymptomatic cases with RP1L1 gene mutations in four families with occult macular dystrophy (OMD). Methods: Four asymptomatic cases from four families were selected from a cohort of 40 subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four asymptomatic cases and three symptomatic patients in the same families were reviewed. The three asymptomatic cases did not have any visual symptoms in either eye, and one was unilaterally affected. Ophthalmologic examinations, including spectral-domain optical coherence tomography (OCT) were performed, and the morphologic characteristics of the photoreceptor layer of the asymptomatic cases were compared to those of the symptomatic patients within the same family. Results: The OCT images demonstrated photoreceptor abnormalities in the parafoveal regions in all of the four asymptomatic cases (i.e., absence of the interdigitation zone and blurring of the ellipsoid zone). However, these microstructures were preserved at the foveal center. The longitudinal reflectivity profiles clearly identified this distinct pattern in the asymptomatic cases. In contrast, no distinct abnormalities were detected by other examinations including perimetry, fundus autofluorescence images, and multifocal electroretinograms (ERGs). Conclusions: The sparing of the central foveal photoreceptor layer accounts for the well-preserved visual acuity in the asymptomatic patients. The sparing may represent either the initial phase of typical OMD or a subtype of macular lesion associated with OMD. It is necessary to examine asymptomatic subjects in families with OMD because some of them may progress to the typical phenotype of OMD.

A Comparison of En Face Optical Coherence Tomography and Fundus Autofluorescence in Stargardt Disease.

Purpose: To compare morphologic changes on en face images derived from wide-field swept-source optical coherence tomography (ssOCT) to hypo- and hyperautofluorescent (hypoAF, hyperAF) areas on short-wavelength autofluorescence (SW-AF), and near-infrared (NIR)-AF in recessive Stargardt disease (STGD1). Methods: Wide-field ssOCT cube scans were obtained from 16 patients (16 eyes). Averaged B-scans and SW-AF images were obtained using Spectralis HRA+OCT. NIR-AF images were obtained from 6 eyes. The inner/outer segment (IS/OS), OS/RPE, and RPE/Bruch's membrane boundaries were segmented, and en face slab images generated. A subRPE slab image was used to measure the abnormal RPE area, and an IS/OS slab image, the IS/OS junction loss area. These were compared to hypo- and abnormal SW-AF areas, and hypoNIR-AF areas. A preRPE(OS) slab image was used to evaluate the spatial and intraretinal locations of flecks. Results: For all eyes, RPE atrophy was visualized as a central hyperreflective area on the subRPE slab, and IS/OS junction loss as an abnormal reflective area on the IS/OS slab; the latter was significantly larger (P = 0.04). There was good agreement between the hyperreflective area on the subRPE slab image and hypoSW-AF area, and between the abnormal reflective area on the IS/OS slab and hypo-hyperSW-AF area; the hypoNIR-AF area indicated that the hyperreflective area on the subRPE slab underestimated RPE atrophy. The spatial locations of hyperreflective flecks on the en face preRPE(OS) slab image corresponded to those on the SW-AF images. Conclusions: Wide-field en face OCT imaging has the potential to be a clinically useful tool for the management of STGD1.

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.

Development of Refractive Errors-What Can We Learn From Inherited Retinal Dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: Study Population: Total of 302 patients with IRD from 2 ophthalmogenetic centers in the Netherlands. Reference Population: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P < .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE -2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development.