High Dynamic Range Image Processing for Retinal Color Fundus Photography.

BACKGROUND AND OBJECTIVE: Color fundus photography is an important imaging modality that is currently limited by a narrow dynamic range. We describe a post-image processing technique to generate high dynamic range (HDR) retinal images with enhanced detail. PATIENTS AND METHODS: This was a retrospective, observational case series evaluating fundus photographs of patients with macular pathology. Photographs were acquired with three or more exposure values using a commercially available camera (Topcon 50-DX). Images were aligned and imported into HDR processing software (Photomatix Pro). Fundus detail was compared between HDR and raw photographs. RESULTS: Sixteen eyes from 10 patients (5 male, 5 female; mean age 59.4 years) were analyzed. Clinician graders preferred the HDR image 91.7% of the time (44/48 image comparisons), with good grader agreement (81.3%, 13/16 eyes). CONCLUSIONS: HDR fundus imaging is feasible using images from existing fundus cameras and may be useful for enhanced visualization of retinal detail in a variety of pathologic states. [Ophthalmic Surg Lasers Imaging Retina 2024;55:263-269.].

Modeling rod and cone photoreceptor cell survival in vivo using optical coherence tomography.

Many retinal diseases involve the loss of light-sensing photoreceptor cells (rods and cones) over time. The severity and distribution of photoreceptor loss varies widely across diseases and affected individuals, so characterizing the degree and pattern of photoreceptor loss can clarify pathophysiology and prognosis. Currently, in vivo visualization of individual photoreceptors requires technology such as adaptive optics, which has numerous limitations and is not widely used. By contrast, optical coherence tomography (OCT) is nearly ubiquitous in daily clinical practice given its ease of image acquisition and detailed visualization of retinal structure. However, OCT cannot resolve individual photoreceptors, and no OCT-based method exists to distinguish between the loss of rods versus cones. Here, we present a computational model that quantitatively estimates rod versus cone photoreceptor loss from OCT. Using histologic data of human photoreceptor topography, we constructed an OCT-based reference model to simulate outer nuclear layer thinning caused by differential loss of rods and cones. The model was able to estimate rod and cone loss using in vivo OCT data from patients with Stargardt disease and healthy controls. Our model provides a powerful new tool to quantify photoreceptor loss using OCT data alone, with potentially broad applications for research and clinical care.

Retinal Sublayer Analysis in Autoimmune Retinopathy and Identification of New Optical Coherence Tomography Phenotypes.

PURPOSE: Autoimmune retinopathy (AIR) is a poorly characterized disease with a wide phenotypic spectrum, complicating investigations of its underlying pathophysiology. We sought to analyze optical coherence tomography (OCT) retinal thickness changes in AIR patients. METHODS: A retrospective chart review from 2007 to 2017 was performed evaluating AIR patients at a single academic, tertiary referral center. OCT retinal sublayer analysis was performed, and paradoxical thickening phenotypes were reviewed. RESULTS: Twenty-nine AIR patients with positive anti-retinal antibodies and OCT imaging were identified. Overall, AIR patients had thinner retinal sublayers compared to controls; however, 12 patients (41.4%) had paradoxical thickening of the outer plexiform layer (OPL). This revealed two distinct OCT phenotypes. No association was found between retinal sublayer thickness and specific antiretinal antibodies. CONCLUSIONS: While the pathogenicity of antiretinal antibodies remains unclear, the OCT phenotypes observed underscore the potential for identifying clues in the underlying disease processes and clinical diagnosis.

Choroidal Neovascularization Is Common in Best Vitelliform Macular Dystrophy and Plays a Role in Vitelliform Lesion Evolution.

OBJECTIVE: Choroidal neovascularization (CNV) is usually considered to be a late-stage complication in Best vitelliform macular dystrophy (BVMD) and can be difficult to diagnose with fluorescein angiography. This study used swept-source (SS) OCT angiography (OCTA) to evaluate the prevalence of CNV in BVMD, identify structural features associated with CNV, and provide insight into the role of CNV in vitelliform lesion evolution. DESIGN: Institutional review board-approved, retrospective, cross-sectional, and longitudinal study. PARTICIPANTS: Patients with molecularly confirmed BVMD. METHODS: Charts from consecutive patients with BVMD imaged with SS-OCTA (PLEX Elite 9000, Carl-Zeiss Meditec Inc) at the University of Iowa from September 2017 to October 2021 were reviewed. Clinical data, including age, gender, best-corrected visual acuity (BCVA), and treatment with intravitreal anti-VEGF injections were recorded. The presence of CNV on SS-OCTA was determined by expert graders and correlated with structural features, such as interstitial fluid, subretinal fluid, nodular subretinal pillar, focal choroidal excavation (FCE), and subfoveal choroidal thickness, with a P value of < 0.05 considered statistically significant. MAIN OUTCOME MEASURES: Presence of CNV on SS-OCTA and correlation with structural features on SS-OCT. RESULTS: A total of 53 eyes from 27 patients (13 women; 48.1%) were included. The mean age was 45 years (range, 8-79 years), and the mean logarithm of the minimum angle of resolution BCVA was 0.38 (range, 0-1). Choroidal neovascularization was identified on SS-OCTA in 27 eyes (50.9%), of which 63.0% had a vitelliform (Gass stage 2) lesion. In 40.7% (11 of 27) of eyes, there was no prior clinical diagnosis of CNV. Other structural features associated with CNV included FCEs (15.1%, 8 of 53 eyes) and nodular pillars (15.1%, 8 of 53 eyes) (P < 0.01). Seven patients had available longitudinal imaging, and most of these patients had CNV visible on SS-OCTA (71.4%; 10 of 14 eyes). CONCLUSION: Choroidal neovascularization is common in BVMD, including in the early stages of the disease. The presence of FCEs or nodular pillars should heighten the clinical suspicion of CNV, which may accelerate vitelliform lesion evolution. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Correlation of features on OCT with visual acuity and Gass lesion type in Best vitelliform macular dystrophy.

OBJECTIVE: To correlate structural features seen on optical coherence tomography (OCT) with best-corrected visual acuity (BCVA) and Gass lesion type in patients with Best vitelliform macular dystrophy (BVMD). METHODS AND ANALYSIS: This is a retrospective case series of consecutive patients with molecularly confirmed BEST1-associated BVMD. OCT scans were reviewed for lesion status and presence of subretinal pillar, focal choroidal excavation (FCE), intraretinal fluid or atrophy. Available OCT angiography images were used to evaluate for the presence of choroidal neovascularisation (CNV). These features were then correlated with BCVA and Gass lesion type. RESULTS: 95 eyes from 48 patients (mean age 38.9 years, range 4-87) were included. The presence of a pillar (24.2%), FCE (20.0%) and atrophy (7.4%) were associated with poor BCVA (p<0.05). Gass lesion type 1 eyes were correlated with good BCVA (LogMAR <0.4) whereas type 5 eyes had poor BCVA (LogMAR >0.4). Among 65 eyes with longitudinal data (mean follow-up 5.1 years), 7 eyes (10.8%) reverted from higher to lower Gass lesion type; of these, 4 eyes (57.1%) had CNV responsive to intravitreal anti-vascular endothelial growth factor treatment. CONCLUSION: OCT-based structural features are readily identifiable in patients with BVMD and have prognostic importance due to their correlation with BCVA.

Analysis of retinal sublayer thicknesses and rates of change in ABCA4-associated Stargardt disease.

Stargardt disease, the most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy. Although clinical trials for Stargardt are currently underway, the disease is typically slowly progressive, and objective, imaging-based biomarkers are critically needed. In this retrospective, observational study, we characterize the thicknesses of individual retinal sublayers by macular optical coherence tomography (OCT) in a large cohort of patients with molecularly-confirmed, ABCA4-associated Stargardt disease (STGD1) relative to normal controls. Automated segmentation of retinal sublayers was performed with manual correction as needed, and thicknesses in various macular regions were compared using mixed effects models. Relative to controls (42 eyes, 40 patients), STGD1 patients (107 eyes, 63 patients) had slight thickening of the nerve fiber layer and retinal pigment epithelium-Bruch's membrane, with thinning in other sublayers, especially the outer nuclear layer (ONL) (p < 0.0015). When comparing the rate of retinal sublayer thickness change over time (mean follow-up 3.9 years for STGD1, 2.5 years for controls), STGD1 retinas thinned faster than controls in the outer retina (ONL to photoreceptor outer segments). OCT-based retinal sublayer thickness measurements are feasible in STGD1 patients and may provide objective measures of disease progression or treatment response.

RETAINED, NONDISSOLVING, TUBULAR FOREIGN BODIES IN THE VITREOUS CAVITY AFTER INTRAVITREAL DEXAMETHASONE (OZURDEX) IMPLANTATION.

PURPOSE: To describe the retention of large, tubular, nondissolving foreign bodies because of a complication of the intravitreal dexamethasone implant (Ozurdex). METHODS: This is a single-center, retrospective chart review of patients who were found to have retained, nondissolvable tubular foreign bodies in the vitreous cavity for more than 6 months (the expected dissolution time of the implants) after Ozurdex injections. Ocular symptomatology and multimodal imaging were reviewed. RESULTS: Five patients had retained, nondissolvable tubular foreign bodies in the vitreous that persisted for months (mean 28.2 months, range 9-67 months) after intravitreal injection of Ozurdex. Two patients were symptomatic due to the foreign bodies and chose alternate local therapy, but none of the patients opted for surgical explantation. CONCLUSION: Persistent, nondissolving, tubular foreign bodies can be seen in the vitreous cavity for years after injection of the Ozurdex implant. Clinicians should be aware of this complication that has the potential to cause visual symptoms and ocular morbidity.

Scleral pits represent degeneration around the posterior ciliary arteries and are signs of disease severity in choroideremia.

BACKGROUND: Choroideremia is an X-linked recessive condition characterized by progressive chorioretinal degeneration. Recently, peculiar scleral ectasias, termed scleral "pits" and "tunnels," have been described as a novel finding in patients with choroideremia, but little is known regarding their etiology or their evolution over time. SUBJECTS: This is a retrospective chart review of consecutive patients with molecularly-confirmed choroideremia and related female carriers seen at a university-based tertiary referral center from January 2010 to July 2016. Multimodal imaging was evaluated for the evolution of scleral pits on fundus photography and scleral tunnels on optical coherence tomography (OCT). The presence of scleral pits and tunnels was correlated with markers of disease severity including age, visual acuity, and severity of visual field loss. RESULTS: Thirty patients (21 affected males, 9 female carriers) were included in the study. Scleral pits were seen in 38.1% (8/21) of affected males and found to occur at insertion sites of the posterior ciliary arteries. Those with scleral pits were older, had poorer visual acuity, and more severe visual field loss than those without (p ≤ 0.05). Scleral tunnels were common (68.4%, 13/19 affected males with available OCT imaging), but no statistically-significant associations with disease severity were seen. The development of new scleral pits and tunnels was observed on longitudinal imaging in 4 and 2 affected males, respectively. No scleral pits or tunnels were visualized in any female carriers. CONCLUSIONS: Scleral pits represent degeneration around the posterior ciliary arteries and may be useful as clinical markers of disease severity in choroideremia.

Wide-Field Swept-Source OCT and Angiography in X-Linked Retinoschisis.

PURPOSE: Retinal vascular and structural changes, particularly outside of the central macula, are not well characterized in X-linked retinoschisis (XLRS). We aim to describe wide-field swept-source OCT (SS-OCT) and swept-source OCT angiography (SS-OCTA) findings in XLRS. DESIGN: Retrospective, cross-sectional study at a tertiary referral center. PARTICIPANTS: Nine consecutive male patients with molecularly confirmed XLRS. METHODS: All patients underwent complete ophthalmic examination with multimodal imaging, including SS-OCT with SS-OCTA (PLEX Elite 9000; Carl-Zeiss Meditec Inc., Dublin, CA). Images were then reviewed by 2 retinal specialists as independent graders to determine the frequency and distribution of retinal structural and vascular abnormalities. MAIN OUTCOME MEASURES: Structural and vascular abnormalities seen on SS-OCT and SS-OCTA in patients with XLRS, with attention to the retinal layers involved, the regional distribution of schitic spaces in the posterior pole, and vascular abnormalities within the superficial and deep capillary plexuses. RESULTS: Eighteen eyes from 9 male patients (mean age, 20 years; range 9-40) with molecularly confirmed XLRS were included. Median best-corrected visual acuity measured 20/63 (range, 20/25-10/300). A total of 17 of 18 eyes (94.4%) were noted to have schitic spaces on SS-OCT, and these were observed to be predominantly within the inner nuclear layer in all 17 eyes. A regional variation in the distribution of cysts was noted, with schitic spaces within the ganglion cell layer (13/17 eyes; 76.5%) observed to be perifoveal and those within the outer nuclear layer (8/17 eyes, 47.1%) observed to be mostly extramacular. All eyes had vascular abnormalities on SS-OCTA, including an irregular foveal avascular zone and flow loss within the deep capillary plexus corresponding to the distribution of the schisis. CONCLUSIONS: Wide-field SS-OCT and SS-OCTA provide detailed visualization of structural and vascular changes in XLRS and may be helpful for monitoring disease progression or treatment response in clinical trials for the disease.

Comparison of retinal and choriocapillaris thicknesses following sitting to supine transition in healthy individuals and patients with age-related macular degeneration.

IMPORTANCE: The effects of position on retinal and choroidal structure are absent from the literature yet may provide insights into disease states such as age-related macular degeneration (AMD). OBJECTIVE: To evaluate the effect of postural change on retinal and choroidal structures in healthy volunteers and patients with non-neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational case series at an academic tertiary care retina service from September 2013 to April 2014 involving 4 unaffected volunteers (8 eyes) and 7 patients (8 eyes) with intermediate AMD. Healthy volunteers selected for the study had no evidence of ocular disease. Patients with AMD were required to have at least 10 intermediate-sized drusen. EXPOSURES: Spectral-domain optical coherence tomography with enhanced depth imaging in upright (sitting) and supine positions. Stable imaging was achieved using a rotating adjustable mechanical arm that we constructed to allow the optical coherence tomography transducer to rotate 90°. The Iowa Reference Algorithms were used to quantify choroid and choriocapillaris thicknesses. MAIN OUTCOMES AND MEASURES: Changes in sitting and supine position central macular thickness (in micrometers), total macular volume (in cubic millimeters), choroidal thickness (in micrometers), and choriocapillaris-equivalent thickness (CCET, in micrometers). RESULTS: Choriocapillaris-equivalent thickness was thinner in healthy participants (9.89 µm; range, 7.15-12.5 µm) compared with patients with intermediate AMD (16.73 µm; range, 10.31-27.38 µm) (P = .02); there was no difference in overall choroidal thickness between the 2 groups (P = .38). There was a 15% CCET reduction among healthy participants when transitioning from a sitting (9.89 µm) to supine (8.4 µm; range, 6.92-10.7 µm) position (P = .02) vs a CCET reduction of 11.1% from sitting (16.73 µm) to supine (14.88 µm; range, 8.76-20.8 µm) positioning (P = .10) in patients with intermediate AMD. CONCLUSIONS AND RELEVANCE: Intermediate AMD appears to be associated with an increase in CCET and with a lack of positional responses that are observed in the CCET of normal eyes. Our results suggest that although outer portions of the choroid do not appear to be responsive to modest positional or hydrostatic pressure, the choriocapillaris capacity is, and this is measurable in vivo. Whether this physiologic deviation that occurs in AMD is related to atrophy, inflammation, or changes in autoregulatory factors or growth factors remains to be determined.

Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study.

BACKGROUND: The purpose of this study was to assess whether differences in central corneal dendritic immune cell densities associated with combinations of soft contact lenses and lens care solutions could be detected by in vivo confocal microscopy. METHODS: Participants were adults naïve to contact lens wear (n = 10) or who wore soft contact lenses habitually on a daily-wear schedule (n = 38) or on a study-assigned schedule for 30 days with daily disposable silicone hydrogel lenses (n = 15). Central corneas were scanned using an in vivo confocal microscope. Cell densities were compared among groups by demographic parameters, lens materials, and lens care solutions (polyhexamethylene biguanide [PHMB], polyquaternium-1 and myristamidopropyl dimethylamine [PQ/MAPD], peroxide, or blister pack solution [for daily disposable lenses]). RESULTS: Among lens wearers, no associations were observed between immune cell densities and age, gender, or years of lens-wearing experience. Mean cell density was significantly lower (P < 0.01) in nonwearers (29 ± 23 cells/mm(2), n = 10) than in lens wearers (64 ± 71 cells/mm(2), n = 53). Mean cell density was lower (P = 0.21) with traditional polymer lenses (47 ± 44 cells/mm(2), n = 12) than with silicone hydrogel lenses (69 ± 77 cells/mm(2), n = 41). Lowest to highest mean density of immune cells among lens wearers was as follows: PQ/MAPD solution (49 ± 28 cells/mm(2)), blister pack solution (63 ± 81 cells/mm(2)), PHMB solution (66 ± 44 cells/mm(2)), and peroxide solution (85 ± 112 cells/mm(2)). CONCLUSION: In this pilot study, in vivo confocal microscopy was useful for detecting an elevated immune response associated with soft contact lenses, and for identifying lens-related and solution-related immune responses that merit further research.

Effects of fluorescein staining on laser in vivo confocal microscopy images of the cornea.

This study was designed to identify whether topical fluorescein, a common ophthalmic tool, affects laser in vivo confocal microscopy of the cornea, a tool with growing applications. Twenty-five eye care specialists were asked to identify presence or absence of fluorescein in 99 confocal micrographs of healthy corneas. Responses were statistically similar to guessing for the epithelium (48% ± 14% of respondents correct per image) and the subbasal nerve plexus (49% ± 11% correct), but results were less clear for the stroma. Dendritic immune cells were quantified in bilateral images from subjects who had been unilaterally stained with fluorescein. Density of dendritic immune cells was statistically similar between the unstained and contralateral stained eyes of 24 contact lens wearers (P = .72) and of 10 nonwearers (P = .53). Overall, the results indicated that fluorescein staining did not interfere with laser confocal microscopy of corneal epithelium, subbasal nerves, or dendritic immune cells.