Foveal Outer Nuclear Layer Thickness Research Articles

Evaluation of changes in macular structures after subthreshold micropulse laser therapy on chronic central serous chorioretinopathy.

To evaluate the changes in macular structures following subthreshold micropulse laser (SHML) treatment for chronic central serous chorioretinopathy (cCSC). Data of 33 eyes from 31 cCSC patients treated with SHML and followed up for at least 6 months has been included in this retrospective study. Main outcome measurements include resolution of subretinal fluid (SRF) and pigment epithelial detachment (PED), the recovery of ellipsoid zone (EZ) continuity, and the foveal outer nuclear layer (ONL) thickness along with its ratio. Mean observation period is 7.355 months (ranging from 6 to 24 months) and mean number of treatments administered is 1.839 (ranging from 1 to 5). 6 months after SHML treatment, there is a significant decrease in the area of SRF and PED (P < 0.001, P = 0.010, respectively). Additionally, the frequency of continuous EZ and the foveal ONL thickness reveal a significant increase (P<0.001, P = 0.005, respectively). The ratio of foveal ONL thickness is significantly higher after laser treatment, particularly in patients with a disease duration of ≤12 months (p = 0.022, P=0.036, respectively). SHML treatment proves to be effective in cCSC eyes, leading to satisfactory recovery of macular structures, especially the photoreceptor layer.

PREVALENCE AND MORPHOLOGIC BIOMARKERS OF METAMORPHOPSIA IN EYES WITH "RESOLVED" CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

To assess relationships between demographics, clinical characteristics, and optical coherence tomography characteristics with persistence of metamorphopsia after resolution of subretinal fluid in eyes with chronic central serous chorioretinopathy. One-hundred participants with "resolved" (absence of subretinal fluid) chronic central serous chorioretinopathy were retrospectively analyzed. Patients underwent a complete ophthalmologic evaluation, including assessment of the presence of metamorphopsia. At the study visit, optical coherence tomography scans were reviewed for qualitative and quantitative features. Sixty-six of 100 patients (66.0%) complained of metamorphopsia. Both the foveal and parafoveal ganglion cell complex thicknesses were thinner in central serous chorioretinopathy eyes with metamorphopsia (35.1 ± 10.6 µ m and 82.0 ± 18.1 µ m vs. 40.7 ± 11.8 µ m and 93.1 ± 13.5 µ m, P = 0.030 and P < 0.0001). In the foveal region, the outer plexiform layer and outer nuclear layer thicknesses were thinner in patients with metamorphopsia (24.6 ± 8.5 µ m and 63.1 ± 20.9 µ m vs. 29.1 ± 8.7 and 76.2 ± 18.2 µ m, P = 0.016 and P = 0.005). The ellipsoid zone band was more frequently discontinued in eyes with metamorphopsia (56.1% vs. 35.3%, P = 0.039). Multivariate stepwise linear regression analysis demonstrated that the strongest associations with the presence of metamorphopsia were with parafoveal ganglion cell complex thickness ( P = 0.004), foveal outer nuclear layer thickness ( P = 0.010), and number of previous recurrences of subretinal fluid accumulation ( P = 0.017). The time interval from the last subretinal fluid resolution was not associated with the presence of metamorphopsia. In "resolved" central serous chorioretinopathy, clinical aspects (i.e., number of previous recurrences) and structural changes (i.e., ganglion cell complex and outer nuclear layer thinning) are associated with metamorphopsia after subretinal fluid resolution.

Outer nuclear layer recovery as a predictor of visual prognosis in type 1 choroidal neovascularization of neovascular age-related macular degeneration

To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.

Visual function and retinal changes after voretigene neparvovec treatment in children with biallelic RPE65-related inherited retinal dystrophy

To report quantitative retinal changes assessed by spectral-domain optical coherence tomography (SD-OCT) in children treated with voretigene neparvovec (VN) at a single center in Italy. Retrospective review of six consecutive pediatric patients with biallelic RPE65-related dystrophy treated bilaterally with VN. SD-OCT scans were analyzed to extract Early Treatment Diabetic Retinopathy Study (ETDRS) thickness maps of the whole retina and the outer nuclear layer (ONL). Changes in visual function were assessed by best-corrected visual acuity (BCVA) and retinal morphology at Days 30/45 and 180. BCVA significantly improved at Day 30/45 and 6 months (both P < 0.001). Central foveal retinal thickness and central foveal ONL thickness tended to increase (6.4 ± 19.2 µm; P = 0.080 and 3.42 ± 7.68 µm; P = 0.091, respectively). ONL thickness of the internal ETDRS-ring significantly increased at day 30/45 (4.7 ± 8.4 µm; P < 0.001) and day 180 (5.0 ± 5.7 µm; P = 0.009). Intra-operative foveal detachment was not associated with a higher function gain in terms of BCVA, but with a mild thinning of foveal ONL after treatment. The improvement of BCVA and thickening of the ONL layer suggest that improvement of visual acuity could be related to partial recovery of retinal morphology in the perifoveal ring.

Changes in the Foveal Outer Nuclear Layer of Central Serous Chorioretinopathy Patients Over the Disease Course and Their Response to Photodynamic Therapy.

Objective:To investigate the association between foveal outer nuclear layer (ONL) thickness and the natural course of central serous chorioretinopathy (CSC), as well as the thickness change after photodynamic therapy (PDT), exploring the PDT timing for CSC.Methods:This retrospective consecutive case series included 358 CSC patients between January 2014 and December 2019. All patients were divided into four groups depending on disease duration: Group A: ≤1 month; Group B: >1 and ≤3 months; Group C: >3 and≤6 months and Group D: >6 months. Foveal ONL thickness of the CSC eye and the clinically healthy fellow eye were measured and compared in all patients. Fifty-six patients were successfully treated with half-dose of PDT, showing complete subretinal fluid absorption, were followed up for more than 6 months and further investigated. The recovery of foveal ONL thickness was analyzed in the affected eyes of patients with different disease duration.Results:No significant reduction was found in CSC foveal ONL thickness (μm) compared to the fellow eye in patients with disease duration less than 1 week (112.3 ± 12.2 vs. 116.7 ± 15.3, P = 0.268). Patients with longer disease duration had varying degrees of ONL thinning compared to the contralateral eye (all P < 0.05) and this difference was more pronounced in patients with disease duration greater than 6 months (75.8 ± 12.9 vs. 113.0 ± 11.5, P < 0.001). At 6-month follow-up after PDT, foveal ONL thickness of patients with <1 month disease duration recovered significantly from onset (97.3 ± 18.2 to 113.6 ± 8.7, P < 0.001) and became similar to that of the healthy fellow eye. Foveal ONL thickness of patients with duration>1 and≤3 months recovered significantly (88.5 ± 11.5 to 95.8 ± 11.3, P = 0.012) but remained thinner than that of the healthy fellow eye. Foveal ONL thickness did not improve significantly in cases with disease duration longer than 3 months (P > 0.05).Conclusion:Foveal ONL thinning was positively associated with disease duration prior to treatment suggesting that longer disease duration limits scope for foveal ONL recovery. CSC patients should be treated with PDT as soon as possible to prevent disease development and reduced visual function.

Foveal Morphology of Normal Fellow Eyes of Patients with Unilateral Macular Hole

To determine the morphology of the fovea in the ophthalmoscopically and tomographically normal fellow eyes of patients with a unilateral idiopathic macular hole (MH) and determine the association between foveal morphological parameters and foveal outer nuclear layer (ONL) thickness. Retrospective observational study. Two hundred three normal fellow eyes of patients with a unilateral MH and 216 normal eyes of 216 healthy subjects. All the eyes were examined using swept-source OCT. A built-in software was used to measure the average retinal and choroidal thickness in the center and in the inner 4 subfields defined in ETDRS. The total retinal thickness, thickness of 3 retinal layers at the fovea and parafovea (0.25 and 0.5 mm nasal and temporal from the fovea), and foveal floor width (FFW) were measured on a scan image of a horizontal line passing through the center of the fovea. We defined the thickness between the internal limiting membrane and outer plexiform layer as inner retinal thickness and the thickness between the external limiting membrane and retinal pigment epithelium as outer retinal thickness. Multiple regression analyses were performed with age, sex, axial length, and the presence of a posterior vitreous detachment as the dependent variables. OCT measurements and correlations between foveal parameters and foveal ONL thickness. The fellow eyes had a thinner central retinal subfield, thinner fovea, thinner ONL at all points except at 0.5 mm nasal, significantly thicker outer retina at all points, and a wider FFW (P= 0.040 to P < 0.0001). The foveal ONL thickness was significantly and positively correlated with the central subfield retinal thickness and foveal thickness and negatively correlated with the FFW (all P < 0.0001). The thinner and deeper fovea and the thinner ONL of the fellow eyes of patients with a unilateral MH make these eyes more susceptible to the formation of an MH.

Threshold thickness of foveal outer nuclear layer associated with outcomes of photodynamic therapy in central serous chorioretinopathy.

To investigate the threshold thickness of the foveal outer nuclear layer (ONL) associated with favourable visual outcome after half-dose photodynamic therapy (PDT) in patients with central serous chorioretinopathy (CSC). The CSC patients were divided into two groups according to whether their best-corrected visual acuity (BCVA) at 1 year after half-dose PDT was 20/20 or worse than 20/20. Three multivariable logistic regression models were respectively created to determine the prognostic value of the pre-PDT foveal ONL thickness, the pre- and the post-PDT foveal ONL thickness ratio, which was defined as the foveal ONL thickness in the CSC eye to that in the normal contralateral eye, for predicting the outcome of half-dose PDT. The areas under the receiver operating characteristic curves (AUCs) were compared and the best cut-off values were determined, respectively. Totally, 134 patients were included. The pre-PDT foveal ONL thickness, the pre-PDT and the post-PDT foveal ONL thickness ratios were all independent predictors of the outcome after half-dose PDT in their respective model (all P < 0.05). The AUC of the post-PDT foveal ONL thickness ratio was significantly higher than the AUCs of the other two parameters (0.940 vs 0.840 and 0.882, DeLong test: both P < 0.05), with the cut-off value of 0.81. The threshold of the foveal ONL thickness ratio is 0.81. Active CSC eyes with a foveal ONL thickness ratio of 0.81 or more could probably retain BCVA of 20/20 after half-dose PDT. They were considered reasonable to wait for spontaneous resolution of sub-retinal fluid.

Microstructural changes after half-dose photodynamic therapy in patients with chronic central serous chorioretinopathy

BackgroundTo evaluate the retinal and choroidal microstructural changes at fovea after half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC), using optical coherence tomography (OCT). MethodsThe study included 35 eyes with unilateral chronic CSC treated with half-dose PDT. The foveal outer nuclear layer (ONL) and subfoveal choroidal thickness (SFCT) in the affected eyes were compared with baseline measurements at month 1, 3, and 6 after half-dose PDT, and those of the healthy contralateral eyes. ResultsThe mean baseline ONL thickness of the affected eyes was thinner compared to unaffected fellow eyes (66.9 ± 16.5 μm vs 111.5 ± 11.6 μm, p<0.001), and increased significantly to 68.6 ± 17.0 μm at month 3 and 68.9 ± 17.3 μm at month 6 after treatment (p = 0.025 and p = 0.014 respectively). The mean baseline SFCT of the affected eyes was thicker compared to unaffected fellow eyes (399.9 ± 87.0 μm vs 338.2 ± 75.4 μm, p<0.001), and decreased significantly after treatment at month 1, 3, and 6 (374.0 ± 84.8 μm, 369.7 ± 81.8 μm, 367.3 ± 80.8 μm respectively, p<0.001 for all). The responder group (n = 26), in which subretinal fluid was completely resorbed, showed a significant increase in ONL thickness and decrease in SFCT after treatment, whereas in the non-responder group (n = 9) ONL thickness and SFCT did not differ after treatment. ConclusionsIn CSC patients, significant changes are observed in foveal ONL thickness and SFCT after half-dose PDT. ONL thickness and SFCT are suggested to be considered in the OCT examinations of CSC patients.

Foveal Therapy in Blue Cone Monochromacy: Predictions of Visual Potential From Artificial Intelligence.

Novel therapeutic approaches for treating inherited retinal degenerations (IRDs) prompt a need to understand which patients with impaired vision have the anatomical potential to gain from participation in a clinical trial. We used supervised machine learning to predict foveal function from foveal structure in blue cone monochromacy (BCM), an X-linked congenital cone photoreceptor dysfunction secondary to mutations in the OPN1LW/OPN1MW gene cluster. BCM patients with either disease-associated large deletion or missense mutations were studied and results compared with those from subjects with other forms of IRD and various degrees of preserved central structure and function. A machine learning technique was used to associate foveal sensitivities and best-corrected visual acuities to foveal structure in IRD patients. Two random forest (RF) models trained on IRD data were applied to predict foveal function in BCM. A curve fitting method was also used and results compared with those of the RF models. The BCM and IRD patients had a comparable range of foveal structure. IRD patients had peak sensitivity at the fovea. Machine learning could successfully predict foveal sensitivity (FS) results from segmented or un-segmented optical coherence tomography (OCT) input. Application of machine learning predictions to BCM at the fovea showed differences between predicted and measured sensitivities, thereby defining treatment potential. The curve fitting method provided similar results. Given a measure of visual acuity (VA) and foveal outer nuclear layer thickness, the question of how many lines of acuity would represent the best efficacious result for each BCM patient could be answered. We propose that foveal vision improvement potential in BCM is predictable from retinal structure using machine learning and curve fitting approaches. This should allow estimates of maximal efficacy in patients being considered for clinical trials and also guide decisions about dosing.

Relationship between photoreceptor layer changes before half-dose photodynamic therapy and functional and anatomic outcomes in central serous chorioretinopathy.

To investigate the relationship between photoreceptor layer (PRL) changes before half-dose photodynamic therapy (PDT) and functional and anatomic outcomes in central serous chorioretinopathy (CSC). Baseline PRL changes were classified based on optical coherence tomography: (1) smooth PRL outer border without a foveal PRL defect; (2) smooth PRL outer border with a foveal PRL defect; (3) granulated PRL outer border and (4) scattered dots of PRL. The best-corrected visual acuity (BCVA), difference in the foveal outer nuclear layer (ONL) thickness between the CSC and normal contralateral eyes and ellipsoid zone (EZ) integrity 12 months after half-dose PDT were compared. In total, 132 patients were included. Group 4 eyes had rather poor BCVA (20/2000-20/400) with little improvement (P = 0.088) at 1 year following half-dose PDT. In the other groups, the mean BCVA improved significantly to 20/25 or better (all P < 0.001). Group 1 eyes had the smallest foveal ONL thickness reduction (-5.12 ± 6.89 μm) and intact EZs (33/33), whereas Group 4 eyes had the largest foveal ONL thickness reduction (-70.00 ± 7.87 μm) and disrupted EZs (4/4). Group 2 and Group 3 eyes behaved similarly: they both had notable foveal ONL thickness reductions (-19.21 ± 18.53 and -20.75 ± 17.62 μm, respectively), but usually continuous EZs (18/19 and 69/76, respectively). The PRL change category before half-dose PDT was closely related to functional and anatomic outcomes. This information could aid clinicians to better determine the timing of treatment with half-dose PDT in CSC.

Inter- and Intra-individual Variations in Foveal Outer Nuclear Layer Thickness and Their Associations with Clinical Characteristics in a Healthy Chinese Population.

Purpose To evaluate foveal outer nuclear layer (ONL) thickness and the difference thereof between bilateral eyes and their possible associations with clinical characteristics in a healthy Chinese population. Materials and Methods Normal subjects were enrolled. Generalized linear models were used to assess the associations of foveal ONL thickness with sex, age, and spherical equivalents (SEs) and the associations of the difference in foveal ONL thickness between bilateral eyes with sex, age, and difference in SEs between bilateral eyes. Results Totally, 304 subjects were included. The average foveal ONL thickness was 103.19 ± 14.25 (range 70–151) μm in the right eye and 103.90 ± 14.63 (range 69–155) μm in the left eye. The mean difference in foveal ONL thickness between right and left eyes was −0.71 ± 4.36 (range −13 to +12) μm. Men had slightly greater foveal ONL thickness values in both right and left eyes compared with women (both P < 0.05); however, some women had a thicker foveal ONL than that of men (85/198 vs. 46/106 in the right eye; 79/198 vs. 52/106in the left eye). Age and SEs were not associated with foveal ONL thickness in either eye (all P > 0.05). Sex, age, and difference in SEs between bilateral eyes were not associated with the difference in foveal ONL thickness between bilateral eyes (all P > 0.05). Conclusions Foveal ONL thickness showed wide variation in a normal Chinese population but little difference between bilateral eyes. Both these parameters could not be adjusted by sex, age, SEs, or the SEs difference between bilateral eyes. Thus, in those diseases involving only one eye, the difference or ratio of foveal ONL thickness between the affected eye and normal fellow eye may reflect the actual degree of the disease, rather than the foveal ONL thickness in the affected eye alone.

Assessing the Interocular Symmetry of Foveal Outer Nuclear Layer Thickness in Achromatopsia.

PurposeWe examine the interocular symmetry of foveal outer nuclear layer (ONL) thickness measurements in subjects with achromatopsia (ACHM).MethodsImages from 76 subjects with CNGA3- or CNGB3-associated ACHM and 42 control subjects were included in the study. Line or volume scans through the fovea of each eye were acquired using optical coherence tomography (OCT). Image quality was assessed for each image included in the analysis using a previously-described maximum tissue contrast index (mTCI) metric. Three foveal ONL thickness measurements were made by a single observer and interocular symmetry was assessed using the average of the three measurements for each eye.ResultsMean (± standard deviation) foveal ONL thickness for subjects with ACHM was 79.7 ± 18.3 μm (right eye) and 79.2 ± 18.7 μm (left eye) compared to 112.9 ± 15.2 (right eye) and 112.1 ± 13.9 μm (left eye) for controls. Foveal ONL thickness did not differ between eyes for ACHM (P = 0.636) or control subjects (P = 0.434). No significant relationship between mTCI and observer repeatability was observed for either control (P = 0.140) or ACHM (P = 0.351) images.ConclusionsWhile foveal ONL thickness is reduced in ACHM compared to controls, the high interocular symmetry indicates that contralateral ONL measurements could be used as a negative control in early-phase monocular treatment trials.Translational RelevanceFoveal ONL thickness can be measured using OCT images over a wide range of image quality. The interocular symmetry of foveal ONL thickness in ACHM and control populations supports the use of the non-study eye as a control for clinical trial purposes.

The relationship between foveal outer nuclear layer thickness in the active and resolved phases of central serous chorioretinopathy treated with half-dose photodynamic therapy

BackgroundTo investigate the relationship between the foveal outer nuclear layer (ONL) thickness in the active and resolved phases of central serous chorioretinopathy (CSC), and its possible association with optical coherence tomography (OCT) parameters.MethodsThe medical records of CSC patients treated with half-dose photodynamic therapy (PDT) between August 2011 and October 2017 were reviewed. The difference between the foveal ONL thickness at 12 m after half-dose PDT and that before half-dose PDT was analyzed, and its association with OCT parameters was assessed using generalized linear models.ResultsSixty-two patients were included. The mean difference in foveal ONL thickness was 9.15 ± 8.16 μm. The average ratios of the retinal detachment height to the subretinal space width on horizontal and vertical scans were 0.10 ± 0.04 and 0.12 ± 0.04, respectively. The ratio was independently associated with the degree of increase in the foveal ONL thickness difference on both the horizontal scans (β = 103.684, P = .000) and vertical scans (β = 67.569, P = .000), even after adjusting for potential confounders.ConclusionsThe majority of resolved CSC eyes showed some increase in foveal ONL thickness, and the degree of increase was related to the ratio of the retinal detachment height to the subretinal space width in their active phase. It suggested that the retina is stretched when it becomes detached, and recovers with resolution of the subretinal fluid. Therefore, besides photoreceptor cell death, retinal stretch may contribute to the reduction in foveal ONL thickness in eyes with active CSC.

Adaptive Optics Retinal Imaging in CNGA3-Associated Achromatopsia: Retinal Characterization, Interocular Symmetry, and Intrafamilial Variability.

PurposeTo investigate retinal structure in subjects with CNGA3-associated achromatopsia and evaluate disease symmetry and intrafamilial variability.MethodsThirty-eight molecularly confirmed subjects underwent ocular examination, optical coherence tomography (OCT), and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans were used for evaluating foveal hypoplasia, grading foveal ellipsoid zone (EZ) disruption, and measuring outer nuclear layer (ONL) thickness. AOSLO images were used to quantify peak foveal cone density, intercell distance (ICD), and the coefficient of variation (CV) of ICD.ResultsMean (±SD) age was 25.9 (±13.1) years. Mean (± SD) best corrected visual acuity (BCVA) was 0.87 (±0.14) logarithm of the minimum angle of resolution. Examination with OCT showed variable disruption or loss of the EZ. Seven subjects were evaluated for disease symmetry, with peak foveal cone density, ICD, CV, ONL thickness, and BCVA not differing significantly between eyes. A cross-sectional evaluation of AOSLO imaging showed a mean (±SD) peak foveal cone density of 19,844 (±13,046) cones/mm2. There was a weak negative association between age and peak foveal cone density (r = −0.397, P = 0.102), as well as between EZ grade and age (P = 0.086).ConclusionsThe remnant cone mosaics were irregular and variably disrupted, with significantly lower peak foveal cone density than unaffected individuals. Variability was also seen among subjects with identical mutations. Therefore, subjects should be considered on an individual basis for stratification in clinical trials. Interocular symmetry suggests that both eyes have comparable therapeutic potential and the fellow eye can serve as a valid control. Longitudinal studies are needed, to further examine the weak negative association between age and foveal cone structure observed here.

CORRELATIONS BETWEEN CHANGES IN PHOTORECEPTOR LAYER AND OTHER CLINICAL CHARACTERISTICS IN CENTRAL SEROUS CHORIORETINOPATHY.

To clarify the correlations between changes in the photoreceptor layer (PRL) and other clinical characteristics during central serous chorioretinopathy. Patients with central serous chorioretinopathy with one eye affected were enrolled. Photoreceptor layer appearance within the detached area was evaluated, and its correlations with symptom duration, best-corrected visual acuity, and the difference in the foveal outer nuclear layer thickness between the affected and contralateral eyes were analyzed. A total of 222 patients were included. The PRL outer border appeared either smooth, granulated, or as scattered dots attached to external limiting membrane. These different appearances were associated with elongation in symptom duration (18, 180, and 1,855 days), decreases in best-corrected visual acuity (6/10, 6/15, and 6/120), and increases in the difference of foveal outer nuclear layer thickness (-16, -32, and -60 μm). Among eyes with smooth PRL outer border, which had similar symptom duration, eyes with foveal PRL defect had poorer best-corrected visual acuity and greater reduction in outer nuclear layer thickness than the other eyes (all P = 0.00). Morphologic changes in PRL, best-corrected visual acuity, the reduction in foveal outer nuclear layer thickness, and symptom duration correlate closely but may behave asynchronously. These objective parameters, besides symptom duration, could be helpful when considering the timing of central serous chorioretinopathy treatment.

Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia.

PurposeCongenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM.MethodsHigh-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme.ResultsAnalyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades.ConclusionsThe degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.)

Foveal Photoreceptor Deformation as a Significant Predictor of Postoperative Visual Outcome in Idiopathic Epiretinal Membrane Surgery.

The purpose of this study was to determine whether the outer nuclear layer (ONL) deformation detected by spectral-domain optical coherence tomography (SD-OCT) is correlated with visual acuity before and after surgery in patients with idiopathic epiretinal membrane (ERM). Forty-four eyes of 44 patients who underwent vitreous surgery for treatment of ERM were included. All patients underwent comprehensive ophthalmologic evaluations including measurement of best corrected visual acuity (BCVA) and SD-OCT before and after surgery. The central foveal thickness (CFT), foveal ONL thickness, juxtafoveal ONL plus outer plexiform layer (OPL) thickness, photoreceptor outer segment thickness, and size of the disrupted interdigitation zone (IZ) line were measured. We defined the "photoreceptor deformation index" (PDI) as the ratio of foveal ONL thickness to the juxtafoveal ONL plus OPL thickness. Multiple regression analysis showed that the only significant predictor of preoperative mean logarithm of the minimum angle of resolution (logMAR) BCVA was preoperative CFT (P < 0.0001). Preoperative PDI (P < 0.0001) and disrupted IZ diameter (P = 0.0242) were positively correlated with logMAR at 3 months after surgery. PDI (P < 0.0001) and disrupted IZ diameter (P = 0.0351) were also positively correlated with logMAR BCVA at 6 months after surgery. The only significant predictor of logMAR at 12 months after surgery was preoperative PDI (P < 0.0001). Preoperative PDI was most significantly correlated with postoperative BCVA. These results suggest that PDI is a novel parameter predicting visual outcome after surgery in eyes with ERM.

Retinal Structure and Function in Achromatopsia: Implications for Gene Therapy

To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy. Cross-sectional study. Forty subjects with ACHM. All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined. Photoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype. Forty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n= 15), GNAT2 (n= 4), and PDE6C (n= 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% hadan absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P= 0.77), mean retinal sensitivity (P= 0.21), or fixation stability (P= 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P= 0.84) or between age and foveal ONL thickness (P= 0.12). The lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring the trials' impact.

Photoreceptor layer thickness measurement in normal and glaucomatous eyes with spectral domain OCT

Background Glaucoma is primarily characterized by the damage of retinal ganglion cells in the inner layer.Whether the outer retinal layers are involved is controversial.Although the functional abnormality of the outer retinal layers have been determined,structural studies present difierent outcomes.Objective This study measured and compared photoreceptor layer thickness between normal and glaucomatous eyes using spectral domain optical coherence tomography(OCT). Methods A case-control study was designed.The macular area of 38 eyes from 38 normal volunteers and 48 primary open-angle glaucomatous eyes(POAG)were imaged by spectral domain OCT(SD OCT).The outer nuclear layer(ONL)and inner and outer segments(IS/OS)layer thicknesses in fovea and parafovea(1.5 mm from the fovea) were measured by a single masked observer using an image analysis software (SigmaScan Pro version 5.0).Retinal nerve fiber layer(RNFL)thicknesses of the 86 eyes were measured by Stratus OCT.The photoreceptor layer thicknesses between normal and glaucomatous eyes were compared.The correlation of photoreceptor with RNFL thicknesses was evaluated with linear and non-linear regression models. Results The outer nuclear layer(ONL)thickness in the fovea in normal and glaucomatous eyes were 96.7±10.7μm and 103.7±13.3 μm,respectively,with a significant difference(P=0.011).The inner and outer segments(IS/OS)layer thicknesses in the fovea in the two groups were 59.3±5.5 μm and 59.5±5.5μm,respectively,without significant difference(P=0.890).The outer nuclear layer(ONL)thicknesses in the parafovea in normal and glaucomatous eyes were 70.9±14.0μm and 68.7 ±10.7μm,respectively,(P=0.410).The inner and outer segments(IS/OS)layer thicknesses in the parafovea in the two groups were 45.2±6.4 μm and 43.6±5.5μm,respectively(P=0.228).The relationship between ONL and RNFL thickness was best described with a second order polynomial regression model assoeiation(Y=-0.019X2+2.73X+10.34,R2=0.211,P=0.005). Conclusion The foveal ONL thickness is increased in glaucomatous eyes.The alteration of foveal ON L thickness is associated with the severity of the disease. Key words: Glaucoma; Photoreceptor; Optical coherence tomography

Measurement of Photoreceptor Layer in Glaucoma: A Spectral-Domain Optical Coherence Tomography Study

Objective. To measure and compare photoreceptor layer thickness between normal and glaucomatous eyes using spectral-domain optical coherence tomography (OCT). Methods. Thirty-eight healthy normal volunteers and 47 glaucoma patients were included in the analysis. One eye from each participant was randomly selected for macula imaging by a spectral-domain OCT (3D OCT-1000, Topcon, Tokyo, Japan). The foveal and parafoveal (1.5 mm from the fovea) outer nuclear layer (ONL) and inner and outer segments (IS+OS) layer thicknesses were measured by a single masked observer. The measurements were repeated 3 times in a random sample of 30 normal eyes to determine the repeatability coefficient and intraclass correlation coefficient. Results. The measurement variabilities of photoreceptor thickness were low. The respective intraclass correlation coefficients of ONL and IS+OS thicknesses were 0.96 (95% confidence interval: 0.94–0.98) and 0.82 (95% confidence interval 0.70–0.90). While there were no differences in parafoveal ONL and IS+OS thicknesses between normal and glaucoma groups (P ≤ .410), the foveal ONL thickness was greater in glaucomatous eyes (P = .011) than in normal eyes. Conclusions. Glaucomatous damage may involve structural change in the photoreceptor layer.