DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGING OF MACULAR PATHOLOGY.

PURPOSE: To survey the impact of directional reflectivity on structures within optical coherence tomography images in retinal pathology. METHODS: Sets of commercial optical coherence tomography images taken from multiple pupil positions were analyzed. These directional optical coherence tomography sets revealed directionally reflective structures within the retina. After ensuring sufficient image quality, resulting hybrid and composite images were characterized by assessing the Henle fiber layer, outer nuclear layer, ellipsoid zone, and interdigitation zone. Additionally, hybrid images were reviewed for novel directionally reflective pathological features. RESULTS: Cross-sectional directional optical coherence tomography image sets were obtained in 75 eyes of 58 patients having a broad range of retinal pathologies. All cases showed improved visualization of the outer nuclear layer/Henle fiber layer interface, and outer nuclear layer thinning was, therefore, more apparent in several cases. The ellipsoid zone and interdigitation zone also demonstrated attenuation where a geometric impact of underlying pathology affected their orientation. Misdirected photoreceptors were also noted as a consistent direction-dependent change in ellipsoid zone reflectivity between regions of normal and absent ellipsoid zone. CONCLUSION: Directional optical coherence tomography enhances the understanding of retinal anatomy and pathology. This optical contrast yields more accurate identification of retinal structures and possible imaging biomarkers for photoreceptor-related pathology.

Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.

Central posterior hyaloidal fibrosis - A novel optical coherence tomography feature associated with choroidal neovascular membrane.

Purpose: To describe a novel optical coherence tomography (OCT) finding at the vitreomacular interface (VMI), and report its association with advanced choroidal neovascularisation (CNV). Observations: Optical coherence tomography (OCT) scans performed at three retinal imaging centres at Amanat Eye Hospital, Pakistan from May 2016 till May 2021 were reviewed. A specific change at the vitreomacular interface was noted consisting of abnormal hyper reflectivity at the point of attachment of the posterior hyaloid membrane to the foveal center which appears to 'fill in' the foveolar depression.Eight eyes of eight patients were identified. All affected eyes had advanced CNV and persistent vitreofoveolar adhesion. In all eyes, the foveal contour (concavity) was maintained and there was no inner retinal surface wrinkling which differentiates this OCT feature from vitreomacular traction or epiretinal membranes. The authors propose the term Central Posterior Hyaloidal Fibrosis (CPHF) for this specific OCT finding. Conclusions and Importance: Central Posterior Hyaloidal Fibrosis (CPHF) is a newly reported OCT finding associated with advanced CNV, which may represent a possible profibrotic influence of a choroidal neovascular membrane to the overlying posterior hyaloid adhesion.

Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

PURPOSE: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4. DESIGN: Nonrandomized multicenter phase I/IIa clinical trial. METHODS: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment. MAIN OUTCOME MEASURES: The primary end point was ocular and systemic adverse events. The secondary end points were best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, multifocal ERG, color fundus photography, short-wavelength fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: The subretinal injections were well tolerated by all 22 patients across 3 dose levels. There was 1 case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In 1 patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared with the untreated eye. However, in 6 patients, hypoautofluorescent changes were worse in the treated eye than in the untreated eye. Of these, 1 patient had retinal pigment epithelium atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in best-corrected visual acuity, static perimetry, kinetic perimetry, total field hill of vision, full field electroretinogram, or multifocal ERG attributable to the treatment. CONCLUSIONS: Subretinal treatment with EIAV-ABCA4 was well tolerated with only 1 case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on fundus autofluorescence. There was a significant reduction in macular flecks in 1 treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.

Volumetric directional optical coherence tomography.

Photoreceptor loss and resultant thinning of the outer nuclear layer (ONL) is an important pathological feature of retinal degenerations and may serve as a useful imaging biomarker for age-related macular degeneration. However, the demarcation between the ONL and the adjacent Henle's fiber layer (HFL) is difficult to visualize with standard optical coherence tomography (OCT). A dedicated OCT system that can precisely control and continuously and synchronously update the imaging beam entry points during scanning has not been realized yet. In this paper, we introduce a novel imaging technology, Volumetric Directional OCT (VD-OCT), which can dynamically adjust the incident beam on the pupil without manual adjustment during a volumetric OCT scan. We also implement a customized spoke-circular scanning pattern to observe the appearance of HFL with sufficient optical contrast in continuous cross-sectional scans through the entire volume. The application of VD-OCT for retinal imaging to exploit directional reflectivity properties of tissue layers has the potential to allow for early identification of retinal diseases.

Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

PURPOSE: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 µm and <125 µm] or ≥1 large drusen [≥125 µm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. INTERVENTION: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. MAIN OUTCOME MEASURES: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). RESULTS: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. CONCLUSIONS: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

Directional Reflectivity of the Ellipsoid Zone in Dry Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Ellipsoid zone (EZ) reflectivity on optical coherence tomography (OCT) is affected by the orientation of the scanning beam. The authors sought to determine how directional reflectivity changes in dry age-related macular degeneration (AMD). PATIENTS AND METHODS: Retrospective image analysis included 17 control and 20 dry AMD subjects. Directional OCT (D-OCT) was performed using multiple displaced pupil entrance positions. EZ pixel values and apparent incidence angles were measured. RESULTS: EZ reflectivity decreased in off-axis scans in controls (P < .001), AMD areas between drusen (P < .001), and AMD areas overlying drusen (P < .001). The magnitude of decrement in EZ reflectivity was significantly higher when incidence angles exceeded 10° in controls than in AMD areas between drusen (P = .024). CONCLUSION: EZ reflectivity in dry AMD may vary by incident angle of light less than in controls, possibly indicating alteration of photoreceptor orientation or integrity. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:145-152.].

Cognitive decline in older adults: What can we learn from optical coherence tomography (OCT)-based retinal vascular imaging?

INTRODUCTION: Accumulated vascular damage contributes to the onset and progression of vascular dementia and possibly to Alzheimer's disease. Here we evaluate the feasibility and utility of using retinal imaging of microvascular markers to identify older adults at risk of cognitive disease. METHODS: The "Eye Determinants of Cognition" (EyeDOC) study recruited a biracial, population-based sample of participants from two sites: Jackson, MS, and Washington Co, MD. Optical coherence tomographic angiography (OCTA) was used to capture vessel density (VD) from a 6 × 6 mm scan of the macula in several vascular layers from 2017 to 2019. The foveal avascular zone (FAZ) area was also estimated. Image quality was assessed by trained graders at a reading center. A neurocognitive battery of 10 tests was administered at three time points from 2011 to 2019 and incident mild cognitive impairement (MCI)/dementia cases were ascertained. Linear mixed-effects models were used to evaluate associations of retinal vascular markers with cognitive factor score change over time. RESULTS: Nine-hundred and seventy-six older adults (mean age of 78.7 (± 4.4) years, 44% black) were imaged. Gradable images were obtained in 55% (535/976), with low signal strength (66%) and motion artifact (22%) being the largest contributors to poor quality. Among the 297 participants with both high-quality images and no clinically significant retinal pathology, the average decline in global cognitive function factor score was -0.03 standard deviations per year. In adjusted analyses, no associations of VD or FAZ with longitudinal changes in either global cognitive function or with incident MCI/dementia were found. CONCLUSIONS: In this large biracial community sample of older adults representative of the target population for retinal screening of cognitive risk, we found that obtaining high-quality OCTA scans was infeasible in a nearly half of older adults. Among the select sample of healthier older adults with scans, OCTA markers were not predictive of cognitive impairment.

Optical Coherence Tomography Angiography Quality Across Three Multicenter Clinical Studies of Diabetic Retinopathy.

Purpose: To explore optical coherence tomography angiography (OCTA) quality and associated factors in multicenter clinical studies. Methods: OCTA scans were obtained from participants with diabetic retinopathy from three DRCR Retina Network clinical studies using the Optovue AngioVue and ZEISS AngioPlex. Macular (3 × 3 mm and 6 × 6 mm) and optic nerve scans were captured. Quality was assessed by the Casey Reading Center. Scans were considered "poor" if the signal strength index (SSI) was less than 55 (AngioVue) or 7 (AngioPlex) or if excess motion, media opacities, beam defocus, incorrect axial position, or other artifacts were present. Results: Included were 7539 scans from 787 eyes (461 participants). Sixty-one percent of scans were considered "good" (n = 4630). Of the 3 × 3-mm (n = 2294), 6 × 6-mm (n = 2705), and optic nerve scans (n = 2540), 62%, 63%, and 59%, respectively, were good. Differences in percentage of good scans by machine were not identified (61% of 6216 for the AngioVue and 63% of 1323 for the AngioPlex). The primary reason for poor scans was low SSI for the AngioVue (67%) and excess motion for the AngioPlex (47%). Good scans were associated with younger age (60 ± 12 years vs. 65 ± 11 years; P < 0.001), male gender (64% of males had good scans vs. 57% female; P = 0.007), and better visual acuity (ETDRS letter score 86.5 ± 6.4 [approximate Snellen equivalent 20/20] vs. 81.6 ± 9.7 [approximate Snellen equivalent 20/25]; P < 0.001). Conclusions: Scan quality or analysis must be improved for OCTA metrics to be used as outcomes in future research. Translational Relevance: Clinicians and researchers should be aware that poor SSI and artifacts are common issues for OCTA images.

Risk Factors and Disease Course for Blood-Brain Barrier Disruption-Associated Maculopathy.

Importance: Blood-brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understood pigmentary maculopathy. Objectives: To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy. Design, Setting, and Participants: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation. Exposures: Treatment with BBBD therapy for any malignant CNS tumor. Main Outcomes and Measures: Rate and potential risk factors for developing BBBD-associated maculopathy and changes in visual acuity and retinal imaging characteristics after completion of BBBD therapy. Results: Of 283 patients treated with BBBD and chemotherapy for a CNS malignant neoplasm, 68 (mean [SD] age, 46.0 [17.9] years; 25 [38.5%] female) had an ophthalmic examination after starting systemic therapy. After excluding 3 patients because of bilateral media opacities, pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD. The number of BBBD treatment sessions, but not age, CNS malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12-1.50; P = .001). After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye. Conclusions and Relevance: In this case series, an association was found between BBBD-related maculopathy and the number of BBBD treatment sessions, suggesting a dose-dependent effect. In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy. These findings may have important implications for patient education and ophthalmic monitoring.

FINGERPRINT SIGN OF THE HENLE FIBER LAYER.

PURPOSE: To describe the appearance of concentric, fingerprint-like waves within the Henle fiber layer (HFL) using en face optical coherence tomography in patients with tractional pathologies of the retina. METHODS: Retrospective analysis of six eyes of six patients imaged by optical coherence tomography with volumetric slabs positioned at the level of the HFL. RESULTS: Optical coherence tomography data from six patients with tractional vitreoretinal pathology were reviewed. Concentric, fingerprint-like microwaves were visualized through en face optical coherence tomography in all six study eyes at the level of the HFL. This finding resembled the finding of HFL waves previously noted histopathologically from force exerted on this layer. CONCLUSION: In retinal pathologies in which specific physical forces act on the retina, volumetric optical coherence tomography may permit visualization of en face concentric, fingerprint-like hyperreflective rings within the HFL. This "fingerprint sign" may represent a biomechanical consequence of traction on the retina and allow clinical decision making based on improved recognition of the existence of such traction.

Intraoperative optical coherence tomographic findings in patients undergoing subretinal gene therapy surgery.

BACKGROUND: To analyze intraoperative OCT (iOCT) findings during subretinal gene therapy. METHODS: A single-center, retrospective, observational, case series study of twenty one eyes submitted to subretinal gene therapy. Intrasurgical high definition videos were included for analyzes. Cases with absence of iOCT video or unsuccessful bleb creation were excluded. Sharp needle tip (SNT) or blunted needle tip (BNT) and their interaction with neurosensory retina were evaluated. Presence of subretinal air bubbles, visible opened retinotomy, and medication reflux were also correlated and analyzed. RESULTS: Nineteen of twenty-one eyes were included. Of the two excluded eyes, subretinal bleb creation was unsuccessful in one and technical issues prevented OCT image acquisition in the other. Immediately before subretinal injection, needle indention/penetration of the neurosensory retina with temporary indentation of the RPE/choroid was evident in 16 (84%) of the 19 eyes. Complete RPE/choroid indentation was needed with BNT use compared to SNT (p = 0.0114). An open retinotomy was identified in 14 (74%) of 19 eyes at the conclusion of bleb injection and was more commonly associated with SNT (p = 0.0108). CONCLUSIONS: iOCT provides valuable real-time feedback of cross-sectional retinal anatomy during subretinal gene therapy surgeries. The type of needle tip and its use during the gene therapy procedure seems to influence in the bleb creation and presence of visible open retinotomy. Further studies of iOCT findings during gene therapy delivery procedures are likely to help refine the surgical technique.

Bull's eye maculopathy associated with hereditary hemochromatosis.

PURPOSE: To report a case of bull's eye maculopathy, a novel finding in a patient with iron overload secondary to hereditary hemochromatosis with a homozygous mutation of the HFE gene. OBSERVATIONS: A 39-year-old man with recently diagnosed hereditary hemochromatosis undergoing treatment by serial phlebotomy presented with bilateral progressive blurry vision and recent onset of photopsias and headaches. Fundus examination revealed a symmetric bull's eye maculopathy with photoreceptor loss and retinal pigment epithelium transmission defects in the area of speckled hyper- and hypo-pigmentation by multimodal imaging. Full field and multifocal electroretinograms demonstrated generalized rod and cone dysfunction with some central preservation of waveforms. Further systemic work-up revealed low ceruloplasmin, mildly decreased serum copper and zinc levels, and low urinary copper. The patient underwent testing for inherited retinal dystrophies, but was not found to have any known pathogenic gene mutations. His ferritin levels normalized with serial phlebotomy and his retinopathy did not appear to progress over 6 months with normalization of his iron levels. CONCLUSIONS AND IMPORTANCE: We report a case of bull's eye maculopathy in a patient with hereditary hemochromatosis with no previous exposure to iron chelators and no known inherited retinal dystrophy. Ocular involvement in hereditary hemochromatosis is relatively rare. In this case, the patient's low serum ceruloplasmin is thought to have increased the amount of redox-active ferrous iron and potentiated retinal iron toxicity resulting in the observed retinopathy. To the authors' knowledge, this is a potentially novel ocular manifestation of hereditary hemochromatosis.

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR.

Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

Visual Acuity and Foveal Structure in Eyes with Fragmented Foveal Avascular Zones.

PURPOSE: To assess the frequency and impact of abnormal foveal avascular zone (FAZ) topography (i.e., a fragmented FAZ) on visual acuity and foveal anatomic features. DESIGN: Prospective, cross-sectional study from March 2018 through July 2019. PARTICIPANTS: Two-hundred fifty participants were screened from a normative OCT angiography database. Of those, 12 participants were found to have at least 1 eye with a fragmented FAZ. Eight returned for follow-up imaging, along with an additional 3 participants with ocular disease (amblyopia, autosomal recessive bestrophinopathy, premature birth) having a similar FAZ phenotype. METHODS: Follow-up OCT imaging and monocular best-corrected visual acuity (BCVA) were performed for these 11 participants. Twenty-four participants with a clearly defined FAZ were recruited for comparison. A normative database was created measuring parafoveal intercapillary area (PICA) to determine if an FAZ was fragmented. MAIN OUTCOME MEASURES: Monocular BCVA, foveal pit depth, foveal pit area, PICA, outer nuclear layer thickness, foveal inner retinal area, and peak cone density. RESULTS: The frequency of a fragmented FAZ was 4.8% of individuals (12 of 250) or 3.6% of eyes (18 of 500 eyes). A significant difference was found between the control eyes and eyes with fragmented FAZs for foveal pit depth, pit area, and total PICA (P < 0.001, P = 0.002, and P < 0.001, respectively). The presence of a fragmented FAZ did not affect visual acuity. CONCLUSIONS: The presence of a fragmented FAZ seems not to be a rare phenotype in individuals with normal vision. The presence of altered FAZ topography in patients with retinal or systemic disease could negatively impact the accuracy and sensitivity of biomarkers dependent on FAZ identification.

Reliability of Spectral-Domain OCT Ellipsoid Zone Area and Shape Measurements in Retinitis Pigmentosa.

PURPOSE: We investigate the ellipsoid zone (EZ) area and EZ boundary shape measurement reliability and the operability characteristics of two methods of EZ boundary delineation in spectral-domain optical coherence tomography (SD-OCT). METHODS: EZ boundaries in SD-OCT scans of 122 eyes from 64 subjects with autosomal dominant retinitis pigmentosa were delineated by three raters using two methods, termed the profile and en face methods. For each method, we determined the measurement reliabilities for boundary area (EZ area) and boundary shape, percentage of eyes with measurable EZ (measurability), time required, and effect of rater experience. RESULTS: With expert raters, inter- and intrarater area intraclass correlation coefficients (ICCs) were 0.986 and 0.980 (profile) and 0.959 and 0.976 (en face), respectively. In comparison, the corresponding shape ICCs were 0.906 and 0.891 (profile) and 0.845 and 0.885 (en face), indicating lower reliability for the raw measurements (P ≤ 0.01). Only profile method interrater reliability depended on experience. Average measurement times per eye were 8.2 (profile) and 4.1 (en face) minutes. Measurability percentages were 99.2% (profile) and 73.0% (en face). CONCLUSIONS: The slower profile method had better measurability, and with expert raters yielded the best area and shape reliabilities. The faster, but less sensitive, en face method still showed excellent reliability, and was less dependent on experience. Shape analysis reveals the boundary measurements underpinning EZ area have lower reliability than suggested by area analysis. TRANSLATIONAL RELEVANCE: This study provides new reliability perspectives and logistical considerations for the manual measurement procedures that generate EZ area outcome measures.

The Henle Fiber Layer in Albinism: Comparison to Normal and Relationship to Outer Nuclear Layer Thickness and Foveal Cone Density.

Purpose: Directional optical coherence tomography (D-OCT) allows the visualization of the Henle fiber layer (HFL) in vivo. Here, we used D-OCT to characterize the HFL and outer nuclear layer (ONL) in albinism and examine the relationship between true foveal ONL and peak cone density. Methods: Horizontal D-OCT B-scans were acquired, registered, and averaged for 12 subjects with oculocutaneous albinism and 26 control subjects. Averaged images were manually segmented to extract HFL and ONL thickness. Adaptive optics scanning light ophthalmoscopy was used to acquire images of the foveal cone mosaic in 10 subjects with albinism, from which peak cone density was assessed. Results: Across the foveal region, the HFL topography was different between subjects with albinism and normal controls. In particular, foveal HFL thickness was thicker in albinism than in normal controls (P < 0.0001), whereas foveal ONL thickness was thinner in albinism than in normal controls (P < 0.0001). The total HFL and ONL thickness was not significantly different between albinism and controls (P = 0.3169). Foveal ONL thickness was positively correlated with peak cone density in subjects with albinism (r = 0.8061, P = 0.0072). Conclusions: Foveal HFL and ONL topography are significantly altered in albinism relative to normal controls. Our data suggest that increased foveal cone packing drives the formation of Henle fibers, more so than the lateral displacement of inner retinal neurons (which is reduced in albinism). The ability to quantify foveal ONL and HFL may help further stratify grading schemes used to assess foveal hypoplasia.

Plexus-Specific Detection of Retinal Vascular Pathologic Conditions with Projection-Resolved OCT Angiography.

OBJECTIVE: To evaluate the projection-resolved (PR) optical coherence tomography angiography (OCTA) algorithm in detecting plexus-specific vascular abnormalities in retinal pathologies. DESIGN: Cross-sectional observational clinical study. PARTICIPANTS: Patients diagnosed with retinal vascular diseases and healthy volunteers. METHODS: Eyes were imaged using an OCT system operating at 840 nm and employing the split-spectrum amplitude decorrelation algorithm. A novel algorithm suppressed projection artifacts inherent to OCTA. The volumetric scans were segmented and visualized on different plexuses. MAIN OUTCOME MEASURES: Qualitative observation of vascular abnormalities on both cross-sectional and en face PR-OCTA images. RESULTS: Eight illustrative cases are reported. In cases of diabetic retinopathy, retinal vessel occlusion, and retinitis pigmentosa, PR-OCTA detected retinal nonperfusion regions within deeper retinal plexuses not visualized by conventional OCTA. In age-related macular degeneration, cross-sectional PR-OCTA permitted the classification of choroidal neovascularization, and, in a case of retinal angiomatous proliferation, identified a vertical vessel contiguous with the deep capillary plexus. In macular telangiectasia, PR-OCTA detected a diving perifoveal vein and delineated subretinal neovascularization. CONCLUSIONS: Application of PR-OCTA promises to improve sensitive, accurate evaluation of individual vascular plexuses in multiple retinal diseases.